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[(and)-257.9(amphotericin)-260.2(B)-255.6(\(250)-171.4(ng/mL\))-256.8(at)-256.9(37)]TJ /F10 1 Tf 15.4418 0 TD ()Tj /F4 1 Tf .3917 0 TD [(C,)-259(95%)-257.8(air)-258(humidity,)]TJ -15.8334 -1.1116 TD [(and)-442.2(5%)-441(CO)]TJ 7.3823 0 0 6.5614 111.7417 139.9181 Tm (2)Tj 9.843 0 0 9.843 115.4267 141.5621 Tm [(.)-441.2(After)-445.3(the)-442.3(hBMSCs)-447(had)-442.2(formed)-446.7(a)-440(conuent)]TJ -5.4256 -1.1174 TD [(monolayer,)-322.3(the)-315.6(cells)-318.9(were)-318.6(passaged)-322.9(and)-315.5(expanded)-317.6(to)-319.1(obtain)]TJ 0 -1.1116 TD [(enough)-272.7(material.)-282.3(Typically,)-276.4(hBMSCs)-274.2(at)-274.2(passage)-275.8(4)-271.8(t)0(o)-273(6)-271.8(were)]TJ T* [(used)-333.7(in)-336.4(the)-332.9(experiments.)]TJ /F11 1 Tf 8.9663 0 0 8.9663 62.022 83.9622 Tm [(Proliferation)-338.4(of)-330.4(hBMSCs)-339.3(treated)-330.4(with)-336.5(BDNF)]TJ /F4 1 Tf 9.843 0 0 9.843 72 67.5212 Tm [(The)-495.2(proliferation)-500.9(of)-497.5(hBMSCs)-498.8(treated)-501(with)-500.9(BDNF)-496.6(was)]TJ -1.0137 -1.1116 TD [(assessed)-478.1(using)-472(a)-474.6(CCK-8)-475(assay)-474(\(Dojindo,)-474.1(Kumamoto-ken,)]TJ 25.504 67.9242 TD [(Japan\).)-294.4(hBMSCs)-297.2(were)-289.8(seeded)-292.1(on)-290.2(96-well)-298(plates)-291.2(at)-291.5(a)-290.2(density)]TJ 0 -1.1174 TD [(of)-514.8(1.0)]TJ /F10 1 Tf 2.7647 0 TD ()Tj /F4 1 Tf .72 0 TD (10)Tj 7.3823 0 0 6.5614 357.1653 718.5825 Tm (3)Tj 9.843 0 0 9.843 365.896 714.1605 Tm [(cells/well)-516.9(and)-517.1(maintained)-511.5(in)-514.9(a)-509.1(basic)-514.6(culture)]TJ -5.368 -1.1116 TD [(medium)-332.9(\(CM\))-323.1(at)-331.8(37)]TJ /F10 1 Tf 8.2191 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C,)-328.1(95%)-326.9(air)-327.1(humidity,)-324.9(and)-327(5%)-325.8(CO)]TJ 7.3823 0 0 6.5614 533.8203 701.5746 Tm (2)Tj 9.843 0 0 9.843 540.6802 703.2188 Tm (for)Tj -23.1252 -1.1116 TD [(24)-169.2(h.)-465.3(BDNF)-462(\(Aviscera)-469.2(Bioscience,)-469.5(Santa)-462.8(Clara,)-467.4(CA\))-460.2(was)]TJ T* [(added)-244(to)-244.2(the)-240.7(CM)-240.3(at)-239.6(a)-244.2(nal)-241.7(concentration)-244(of)-244.1(50)-238.3(or)-238.3(100)-170.3(ng/mL.)]TJ 0 -1.1174 TD [(After)-272.6(1,)-275.2(3,)-269.5(5,)-269.5(and)-269.4(7)-271.8(days,)-268(the)-269.5(media)-274.1(were)-272.5(replaced)-278.5(with)-270.5(10%)]TJ 0 -1.1116 TD [(CCK-8)-382.8(solution)-377.6(and)-373.1(incubated)-382.3(for)-377.6(4)-168.1(h)-375.5(at)-372.1(37)]TJ /F10 1 Tf 18.1661 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C.)-374.2(The)-380(absor-)]TJ -18.5635 -1.1116 TD [(bances)-372.8(of)-359.3(the)-367.5(formazan-dissolved)-371.1(solutions)-367(were)-370.4(measured)]TJ 0 -1.1174 TD [(using)-339.5(a)-330.6(spectrometer)-341.7(at)-331.8(a)-336.3(wavelength)-338.2(of)-330.5(450)-170.3(nm.)]TJ /F11 1 Tf 8.9663 0 0 8.9663 313.0582 604.6865 Tm 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[(humid)5.6(ity)5.6(,)-238.6(a)-1.3(nd)-236.3(5%)-237.4(CO)]TJ 7.3823 0 0 6.5614 395.5463 553.7195 Tm 0 Tc (2)Tj 9.843 0 0 9.843 401.3857 555.3636 Tm -.0223 Tc [(for)-236.5(2)-.4(4)-161.6(h)-.4(.)-238.8(F)-.2(o)5.4(u)-.4(r)-242.2(e)4.2(xp)5.4(eri)5.3(m)-1.6(ental)-242.4(g)5.4(rou)5.4(p)-.4(s)-236.3(w)-1.2(er)5.4(e)]TJ -8.9736 -1.1116 TD -.0274 Tc [(d)-5.5(e)-6.6(si)-5.6(g)-5.5(n).3(a)-6.6(t).2(e)-6.6(d)-345.3(as)-350.8(\(I)-5.4(\))-345.2(t)-5.6(he)-346.4(C)-6.5(M)-346.2(gr)-5.4(ou)-5.5(p)-5.5(,)-341.9(\()-5.4(I).3(I)-5.4(\))-345.2(o)-5.5(s).5(t)-5.6(e)-6.6(og)-5.5(en)-5.5(i)-5.6(c)-346.4(di)-5.6(ff)-5.4(e)-6.6(r).3(e)-6.6(n)-5.5(ti)-5.6(at)-5.6(i)-5.6(o).3(n)]TJ T* -.0224 Tc [(mediu)5.3(m)-629.5(\(OM\)-)5.3(onl)5.2(y)-634(g)5.3(ro)5.3(up)-628.3(\()]TJ /F6 1 Tf 11.7325 0 TD 0 Tc (a)Tj /F4 1 Tf .5299 0 TD -.0251 Tc [(ME)-4.4(M,)-633.3(10%)-632(F)-3(BS,)-633.3(1)2.6(00)-170.2(U/mL)]TJ -12.2624 -1.1174 TD -.0223 Tc [(pen)5.4(i)-.5(cill)5.3(in,)-480.7(1)-.4(0)5.4(0)]TJ /F6 1 Tf 5.8691 0 TD 0 Tc (m)Tj /F4 1 Tf .5241 0 TD -.0275 Tc [(g)-5.6(/)-5.7(mL)-490.6(s)-5.4(t).1(r)-5.5(e)-6.7(pt)-5.7(om)-6.8(yc)-6.7(i)-5.7(n).2(,)-491.7(2).2(5)-5.6(0)-172.6(ng)-5.6(/m)-6.8(L)-490.6(a)-1(m)-6.8(p).2(h)-5.6(o)-5.6(t).1(e)-6.7(r).2(i)-5.7(c)-6.7(in)]TJ -6.3933 -1.1116 TD -.0222 Tc [(B,)-348.2(50)-167.3(mg/)5.4(m)-1.5(L)-347(a)-1.4(scor)5.5(bic)-347(aci)5.4(d,)-348.2(10)-161.5(mM)-346.7(gly)5.5(c)-1.4(erol)5.4(-2-)5.5(p)-.3(h)5.5(o)-.3(sp)5.5(hate,)-348.2(a)-1.4(n)5.5(d)]TJ T* -.0232 Tc [(100)-162.5(nM)-365(dexamethason)4.5(e\))4.5(,)-366.4(\(II)4.5(I\))-364.1(a)-371(5)4.5(0)-168.3(n)-1.3(g)4.5(/)-1.4(mL)-371.1(BDNF)]TJ /F10 1 Tf 19.3814 0 TD 0 Tc (+)Tj /F4 1 Tf .5299 0 TD -.0233 Tc [(OM)-365.1(gro)4.4(up,)]TJ -19.9113 -1.1174 TD -.0215 Tc [(a)-6.5(n).4(d)-299.1(\()-5.3(IV\))-299(a)-306(100)-172.3(ng/)-5.5(mL)-300.3(BDN)-6.2(F)]TJ /F10 1 Tf 11.41 0 TD 0 Tc (+)Tj /F4 1 Tf .5299 0 TD -.0214 Tc [(O)-6.1(M)-299.9(gr)-5.2(oup)-5.2(.)-295.5(O)-6.1(n)-299(d).5(ay)-299(7)-5.2(,)-295.5(h)-5.2(B)-.5(MS)-5.1(Cs)]TJ -11.9399 -1.1116 TD -.0218 Tc [(w)-6.5(e)-1(r)-5.6(e)-179.6(ly)-5.6(sed)-184.2(w)-.7(it)-5.7(h)-178.4(R)-.9(I)-5.6(P).3(A)-185(l)0(ys)-5.4(is)-184(buf)-5.6(fer)-184.1(\().2(S)-5.5(o).1(la)-6.8(rbi)-5.7(o).1(,)-180.7(B)-.9(e)-6.8(iji)-5.8(ng)-5.6(,)-175(C)-6.6(hin)-5.6(a)-1(\))-184.1(a)-1(nd)]TJ T* -.0214 Tc [(c)-6.4(e)-.6(ll)-230(l)-5.3(y).5(sa)-6.4(tes)-229.7(w)-.3(e)-6.4(r).6(e)-231(cen)-5.2(tr)-5.2(ifu)-5.2(g).5(ed)-229.8(at)-230(12)-5.2(,000)]TJ /F5 1 Tf 14.8716 0 TD 0 Tc (g)Tj /F4 1 Tf .7084 0 TD -.0217 Tc [(for)-230.1(4)-166.8(m)-6.7(i).1(n.)-232.5(The)-231.3(a)-.9(lk)-5.5(ali)-5.6(n).2(e)]TJ -15.58 -1.1116 TD -.0179 Tc [(ph)4(os)4.2(p)4(h)-1.7(at)3.9(as)4.2(e)-313.9(\()4.1(ALP)4.2(\))-312.7(act)3.9(i)-1.8(v)4(i)-1.9(t)3.9(i)3.9(e)-2.9(s)-312.5(o)4(f)-312.7(t)3.9(he)-313.9(t)3.9(r)-1.7(eated)-312.7(h)4(B)3(MS)4.2(Cs)-312.5(were)-308.1(de-)]TJ 0 -1.1174 TD -.017 Tc [(termi)4.8(n)4.9(ed)-432.8(us)5.1(i)4.8(n)-.8(g)-432.8(a)-439.7(p)4.9(-)5(ni)4.8(tr)5(o)4.9(p)-.8(h)4.9(e)3.8(ny)4.9(l)-438.7(p)4.9(h)4.9(o)-.8(s)5.1(p)4.9(hat)4.8(e)-439.7(\()5(P)-.7(NP)5.1(P\))-432.8(ki)4.8(t)-438.7(\()-121.7(J)5.1(i)4.8(an)4.9(-)]TJ 0 -1.1116 TD -.0215 Tc [(c)-6.5(h).4(en)-5.3(g)-402.7(B)-.6(io)-5.3(eng)-5.3(i).3(n)-5.3(eer)-5.3(ing)-402.7(I)-5.3(ns)-5.1(tit)-5.5(ute)-6.5(,)-399.3(N)-6.2(a)-.7(nj)-5.5(ing)-5.3(,)-399.3(C)-6.4(h).4(in)-5.3(a\).)-405.1(O)-.4(n)-402.7(d)-5.3(ay)-402.7(14)-5.3(,)]TJ T* [(h)-5.2(B)-.5(MS)-5.1(Cs)-223.9(we)-6.4(re)-225.2(x)-5.2(ed)-224.1(wi)-5.3(th)-224.1(95)-5.2(%)-219.4(a)-6.4(lco)-5.2(hol)-224.2(a)-6.4(n).5(d)-224.1(s).7(t)-5.3(a)-.6(in)-5.2(ed)-224.1(wi)-5.4(th)-224.1(ali)-5.3(zar)-5.2(in)]TJ 0 -1.1174 TD -.0217 Tc [(r)-5.5(e)-.9(d)-264.7(S)-258.8(t)-5.6(o)-258.9(r)-5.5(e)-.9(vea)-6.7(l)-259.1(b)-5.5(one)-265.9(no)-5.5(dul)-5.6(es)-264.5(\(Si)-5.6(g).2(ma)-6.7(-Al)-5.6(d).2(ri)-5.7(ch,)-267(S).4(t.)-261.3(L)-6.7(oui)-5.7(s,)-261.3(M)-6.4(O)-.6(\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 313.0582 380.1826 Tm 0 Tc [(Relative)-335.5(ALP)-335.3(gene)-333.8(expression)]TJ /F4 1 Tf 9.843 0 0 9.843 323.0361 363.7416 Tm [(hBMSCs)-452.7(w)15.3(e)15(r)16.2(e)-434.2(s)16.4(e)0(e)24.3(d)16.2(e)15(d)-433.1(o)16.2(n)-433.1(s)16.4(i)16.1(x-)26.6(w)15.3(e)15(l)16(l)-433.2(p)16.2(l)0(a)25.3(t)16.1(e)15(s)-432.9(a)15(t)-433.2(a)-434.2(d)16.2(e)15(n)16.2(si)26.7(t)16(y)-433.1(o)16.2(f)]TJ -1.0137 -1.1116 TD [(2.)30(0)]TJ /F10 1 Tf 1.3766 0 TD ()Tj /F4 1 Tf .7027 0 TD -.0162 Tc (10)Tj 7.3823 0 0 6.5614 343.0487 357.1653 Tm 0 Tc (5)Tj 9.843 0 0 9.843 350.3621 352.7999 Tm -.0156 Tc [(cell)-15.6(s)11.1(/wel)-15.6(l)-369.4(a)-.6(nd)-385.3(maint)-15.6(a)9.7(i).4(ned)-385.3(i).4(n)-379.6(C)-15.6(M)-371.1(a)-.6(t)-379.7(3)-15.6(7)]TJ /F10 1 Tf 15.6549 0 TD 0 Tc ()Tj /F4 1 Tf .3801 0 TD -.0157 Tc [(C,)-382(95%)-386.5(air)]TJ -19.8249 -1.1116 TD -.0159 Tc [(h)-15.9(u)10.7(midit)-15.9(y)10.6(,)-387.9(a)-.9(nd)-391.4(5%)-386.7(CO)]TJ 7.3823 0 0 6.5614 401.2723 340.2141 Tm 0 Tc (2)Tj 9.843 0 0 9.843 408.6424 341.8582 Tm -.0156 Tc [(fo)-15.6(r)-374.9(2).6(4)-166.4(h)-15.6(.)-377.2(B)-.4(ased)-391.1(on)-385.3(t)-15.6(h)10.9(e)-386.5(A)-.3(LP)-390.9(acti)-15.6(v)10.9(ity)]TJ -9.7109 -1.1174 TD [(a)-15.7(n)9.7(d)-235.7(m)-.7(inera)-15.7(l)9.6(ized)-235.7(nod)-15.7(u)10.9(l).4(e)-236.8(a)-.7(ssay)-15.7(s)11.1(,)-232.2(o).5(n)-15.7(l)10.8(y)-235.7(a)-231.1(co)-15.7(n)10.9(cent)-15.7(r)10.8(atio)-15.7(n)-219.5(o).5(f)-235.6(1).5(0)-15.7(0)-156.1(ng/)]TJ 0 -1.1116 TD -.0153 Tc [(m)-15.3(L)-244.6(BDNF)-258.1(was)-258.1(u).9(sed)-258.3(t).8(o)-252.5(a)-15.3(s)10.3(s)1.1(es)-15.3(s)]TJ /F5 1 Tf 11.8708 0 TD -.0157 Tc (ALP)Tj /F4 1 Tf 1.9929 0 TD [(gene)-260(expre)-15.8(s)9.8(s).6(io)-15.8(n)10.8(.)-255.4(The)-254.2(t)-15.8(h)10.7(r).4(ee)]TJ -13.8636 -1.1116 TD -.0159 Tc [(e)-15.9(x)9.5(peri)-15.9(m)9.3(e)-.9(ntal)-316.6(gro)-15.9(u)10.7(p).3(s)-316.3(a)-.9(sses)-15.9(s)11.1(ed)-316.5(were)-317.7(\(I\))-316.5(the)-317.7(C)-.8(M)-311.6(g)-15.9(r)10.7(oup,)-313.1(\()-15.9(I)10.8(I\))-316.5(the)]TJ 0 -1.1174 TD [(O)-16(M)8.8(-onl)-16(y)-323.6(group)-16(,)-320(a)-1(n)-16(d)-323.5(\(III)-16(\))-323.4(a)-335(100)-166.8(ng/)-16(m)9.2(L)-335.1(BDNF)]TJ /F10 1 Tf 18.3504 0 TD 0 Tc (+)Tj /F4 1 Tf .5357 0 TD -.0162 Tc [(O)-16.2(M)-325.4(group)-16.2(.)]TJ -17.8724 -1.1116 TD 0 Tc [(On)-365.9(day)-361.6(3,)-367.4(total)-364.2(RNA)-363.2(was)-368(isolated)-362.7(with)-362.6(TRIzol)-367.2(\(Invitro-)]TJ -1.0137 -1.1116 TD [(gen\))-495.1(and)-494(quantied)-496.2(by)-491.8(spectrometry)-496(at)-493.1(260)-492.9(and)-494(280)-164.6(nm.)]TJ 0 -1.1174 TD [(cDNA)-238.6(was)-235.5(reverse)-241.3(transcribed)-240.2(using)-235.8(2)]TJ /F6 1 Tf 15.5166 0 TD (m)Tj /F4 1 Tf .5529 0 TD [(g)-237.2(RNA)-236.5(template)-238.5(and)]TJ -16.0696 -1.1116 TD [(a)-532.1(M-MLV)-533.5(reverse)-535.1(transcriptase)-531.5(\(Thermo)-535.4(Scientic;)-533.1(Life)]TJ T* [(Technologi)-9(es,)-455.9(Carlsbad,)-459(CA\))-460.2(in)-457.3(a)-457.3(total)-456.3(volume)-458.4(of)-457.2(20)]TJ /F6 1 Tf 22.8776 0 TD (m)Tj /F4 1 Tf .5529 0 TD (L.)Tj -23.4305 -1.1174 TD [(Each)-486(real-time)-487.3(polymerase)-482.2(chain)-486(reaction)-484.8(\(RT-PCR\))-479.4(was)]TJ 0 -1.1116 TD [(performed)-549(in)-543.7(duplicate)-543.7(using)-546.9(1)]TJ /F6 1 Tf 13.6563 0 TD (m)Tj /F4 1 Tf .5472 0 TD [(L)-543.7(cDNA)-549.6(template)-543.8(in)-543.7(a)]TJ -14.2034 -1.1116 TD (20)Tj /F6 1 Tf 1.1692 0 TD (m)Tj /F4 1 Tf .5529 0 TD [(L)-313.3(reaction)-317.8(volume)-314.4(with)-310.8(200)-164.6(nmol/L)-314.6(of)-313.2(each)-318.9(primer)-314.3(and)]TJ -1.7222 -1.1116 TD [(a)-307.5(FastStart)-311.6(Universal)-306.9(SYBR)-306.7(Green)-308.2(PCR)-304.7(master)-309.6(mix)-304.2(\(ROX\))]TJ 0 -1.1174 TD [(\(Roche)-574.4(Life)-571.3(Science,)-574.5(Penzberg,)-574.2(Germany\).)-569.5(The)-570.1(thermal)]TJ 0 -1.1116 TD [(cycling)-258(conditions)-260(were)-261(an)-251(initial)-257.2(step)-258.9(of)-255.6(50)]TJ /F10 1 Tf 17.6247 0 TD ()Tj /F4 1 Tf .3917 0 TD [(C)-255.6(for)-256.7(2)-168.1(min)-258.1(and)]TJ -18.0164 -1.1116 TD (95)Tj /F10 1 Tf 1.0022 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C)-267.1(for)-268.2(10)-169.2(min,)-267.3(followed)-270.3(by)-267.1(40)-267.1(cycles)-275(of)-267.1(94)]TJ /F10 1 Tf 16.8644 0 TD ()Tj /F4 1 Tf .3917 0 TD [(C)-272.8(for)-268.2(15)-163.5(s)-271.6(and)]TJ -18.6557 -1.1174 TD (60)Tj /F10 1 Tf 1.0022 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C)-457.1(for)-458.3(1)-168.1(min.)-457.4(Reactions)-463.8(were)-462.6(performed)-462.6(using)-454.7(an)-464.1(ABI)]TJ -1.3996 -1.1116 TD [(PRISM)-548.5(7500)-540.1(Sequence)-549(Detection)-550.3(System)-544.4(\(Applied)-546.7(Bio-)]TJ T* [(systems,)-341.4(Foster)-335.8(City,)-331.7(CA\).)]TJ 1.0137 -1.1174 TD [(Glyceraldehyde-3-phosphate)-826.9(dehydrogenase)-819.4(\()]TJ /F5 1 Tf 19.56 0 TD (GAPDH)Tj /F4 1 Tf 3.3867 0 TD (\))Tj -23.9604 -1.1116 TD [(was)-460.2(used)-460.4(as)-452.4(an)-458.4(internal)-460.8(control.)-456(The)-460.7(sense)-456.7(and)-453.7(antisense)]TJ T* [(primers)-568.7(used)-564.1(to)-561(detect)]TJ /F5 1 Tf 10.3329 0 TD (ALP)Tj /F4 1 Tf 2.3442 0 TD [(mRNA)-567.1(were)]TJ /F5 1 Tf 5.9613 0 TD (ACTGGTACT)Tj -18.6384 -1.1116 TD [(CAGACAACGAGA)-14.6(T)]TJ /F4 1 Tf 8.6453 0 TD (and)Tj /F5 1 Tf 1.6991 0 TD (ACGTCAATGTCCCTGATGTTAT)Tj /F4 1 Tf 13.7023 0 TD (,)Tj -24.0468 -1.1174 TD .0202 Tc [(respectively.)-536.2(The)-535(s)2(e)-5.1(n)1.8(se)-540.8(and)-533.8(a)]TJ 13.3798 0 TD .0188 Tc [(nti)-5.5(s).6(en)-5.3(se)-536.4(p)-5.3(r).5(ime)-6.5(r).5(s)-540.8(u).4(sed)-541(t).3(o)]TJ -13.3798 -1.1116 TD .0207 Tc [(det)2.2(e)-4.6(ct)]TJ /F5 1 Tf 3.0872 0 TD .0193 Tc [(GA)-6(PDH)]TJ /F4 1 Tf 4.0433 0 TD .0197 Tc [(mR)-5.5(NA)-558.2(control)-557.5(g)-4.4(ene)-558.5(w)-5.3(ere)]TJ /F5 1 Tf 12.1875 0 TD .0202 Tc [(A)-5.1(C).8(AACTTT)]TJ -19.3181 -1.1116 TD 0 Tc [(GGTAT)-8.1(CGTGG)-9(AAGG)]TJ /F4 1 Tf 9.6072 0 TD .0218 Tc (and)Tj /F5 1 Tf 1.9007 0 TD .0194 Tc [(GCC)-5.8(A)-.2(TCAC)-5.8(GCCA)-5.9(CAGTTTC)]TJ /F4 1 Tf 12.5389 0 TD 0 Tc (,)Tj /F8 1 Tf 8.9663 0 0 8.9663 62.022 749.6502 Tm (1284)Tj 49.4894 0 TD [(LIU)-334.5(ET)-338.7(AL.)]TJ ET endstream endobj 47 0 obj <>stream /GS1 gs BT /F4 1 Tf 9.843 0 0 9.843 59.7543 725.1588 Tm 0 0 0 rg 0 Tc 0 Tw [(re)14(sp)21(ec)18.5(ti)20.6(ve)19.7(ly)20.7(.)-337.5(R)0(e)18.6(l)0(a)19.5(t)0(i)20.6(v)0(e)-325.9(m)0(R)18.6(N)0(A)-326.5(e)0(x)19.7(p)0(r)20.9(e)0(s)19.9(s)0(i)20.9(o)0(n)-324.7(w)0(a)18.8(s)-335(as)19.9(se)14.1(ss)21.2(ed)-325.9(us)21(in)20.7(g)]TJ 0 -1.1174 TD [(th)15(e)]TJ /F6 1 Tf 1.5321 0 TD (DD)Tj /F4 1 Tf 1.3132 0 TD [(Ct)-314.4(me)18.4(th)15(od)20.8(.)]TJ 7.3823 0 0 6.5614 131.5842 718.5825 Tm (29)Tj /F11 1 Tf 8.9663 0 0 8.9663 59.7543 686.7778 Tm [(Knockdown)-338(of)-330.4(TrkB)-334(and)-335.7(the)-334.8(osteogenic)-329.5(mechanism)]TJ 0 -1.2266 TD [(of)-336.7(BDNF)]TJ /F4 1 Tf 9.843 0 0 9.843 69.7323 659.3384 Tm [(hBMSCs)-452.7(w)15.3(e)15(r)16.2(e)-434.2(s)16.4(e)15(ed)25.4(e)15(d)-433.1(o)16.2(n)-433.1(s)16.4(i)16.1(x)16.2(-)0(w)25.8(e)15(l)16.1(l)-433.2(p)16.2(l)16.1(at)25.3(e)15(s)-432.9(a)15(t)-433.2(a)-434.2(d)16.2(e)15(n)16.2(si)26.7(t)16.1(y)-433.1(o)16.2(f)]TJ -1.0137 -1.1116 TD [(2.)30(0)]TJ /F10 1 Tf 1.3708 0 TD ()Tj /F4 1 Tf .7084 0 TD -.0162 Tc (10)Tj 7.3823 0 0 6.5614 89.7448 652.7621 Tm 0 Tc (5)Tj 9.843 0 0 9.843 97.0582 648.3967 Tm -.0156 Tc [(cell)-15.6(s)11.1(/wel)-15.6(l)-369.4(a)-.6(nd)-385.3(maint)-15.6(a)9.7(i).5(ned)-385.3(i).5(n)-379.6(C)-.4(M)-386.2(a)-.6(t)-379.7(3)-15.6(7)]TJ /F10 1 Tf 15.6549 0 TD 0 Tc ()Tj /F4 1 Tf .3801 0 TD -.0157 Tc [(C,)-382(95%)-386.5(air)]TJ -19.8249 -1.1116 TD 0 Tc [(hu)26.6(m)15(i)16.1(d)16.2(i)16.1(ty)26.5(,)-228.1(a)15(nd)-215.3(5%)-216.4(C)15.2(O)]TJ 7.3823 0 0 6.5614 143.7732 635.8109 Tm (2)Tj 9.843 0 0 9.843 149.7826 637.455 Tm -.0158 Tc [(for)-247.2(24)-166.6(h)-15.8(.)-233.4(BMSC)-15.8(s)-231.9(w)-15.8(e)8.8(r).4(e)-248.4(t).3(ran)-15.8(s)11(fect)-15.8(e)9.5(d)-241.5(w)-15.8(i)9.8(th)]TJ -9.1464 -1.1174 TD [(s)-15.8(i)10.9(RNA-)-15.8(T)9.6(rkB)-530.5(\(sens)-15.8(e)]TJ /F5 1 Tf 8.5301 0 TD -.0153 Tc [(GU)-15.3(G)9.6(A)-.3(UCCGG)-15.3(U)9.6(UCCUAA)-15.3(U)9.2(A)-.3(UTT)]TJ /F4 1 Tf 14.3474 0 TD -.0156 Tc (and)Tj -22.8776 -1.1116 TD 0 Tc [(an)25.4(t)16.1(i)16.1(s)16.4(en)25.4(s)16.4(e)]TJ /F5 1 Tf 4.2161 0 TD -.0269 Tc [(A)-6.1(U)-.1(A)-6.1(UUA)-6.1(GGA)-6.1(AC)-6(CGG)-5.8(A)-.4(UC)-6(AC)-6(TT)]TJ /F4 1 Tf 13.2934 0 TD -.0262 Tc [(;)-678.3(G)-5.1(ene)-679.3(P)-4.1(harma,)]TJ -17.5095 -1.1116 TD -.0257 Tc [(C)-4.8(h)2(ina\))-337.8(or)-337.8(a)-333.2(n)-3.8(ega)-4.9(t)1.9(ive)-339(c).8(ontrol)-337.9(using)-337.8(L).8(ipofec)-4.9(ta)-4.9(mine)-333.2(2000)-337.8(Trans-)]TJ 0 -1.1174 TD -.0273 Tc [(f)-5.3(e)-.8(c)-6.5(t).3(i)-5.5(o).4(n)-310.6(r).4(e)-6.5(a)-.8(ge)-6.5(nt)-310.8(\(T)-6.5(he)-6.5(rmo)-310.6(F)-5.2(is)-5.2(her)-310.6(s)-5.2(ci)-5.5(ent)-5.5(i).3()-5.2(c)-.8(\))-310.6(a)-.8(t)-310.8(a)-311.8(co)-5.4(nce)-6.5(n).4(t)-5.5(r).4(a)-6.5(tio)-5.4(n)-310.6(o).4(f)]TJ 0 -1.1116 TD -.027 Tc [(1)-5.1(0).7(0)-172.1(n).7(M/)-5.2(we)-6.2(ll)-5.2(.)-410.6(C)-.3(e)-6.2(l).6(l)-5.2(s)-413.8(wer)-5(e)-415.2(th)-5.1(en)-414(tr)-5(eat)-5.2(ed)-414(w)-5.9(ith)-414(1)-5.1(0).7(0)-172.1(ng/)-5.2(mL)-415.2(BD)-5.9(NF)]TJ T* -.0274 Tc [(a)-6.6(n).3(d)-402.9(c)-.9(u)-5.5(ltu)-5.5(re)-6.6(d)-397.1(f)-5.4(or)-402.8(48)-166.7(h)-402.9(a)-.9(n)-5.5(d)-397.1(t)-5.6(h).3(e)-404(t).2(ot)-5.6(al)-403(RN)-6.3(A)-398(w)-.6(a)-6.6(s)-396.9(c)-6.6(o).3(l)-5.6(l).2(ec)-6.6(te)-6.6(d)-397.1(u)-5.5(si)-5.6(ng)]TJ T* [(T)-6.7(R)-.8(I)-5.5(z)-1(ol)-380.1(\(I)-5.5(nv)-5.6(it)-5.7(ro)-5.6(gen)-5.6(\))-374.1(a)-6.7(s)-374(d)-5.6(e)-1(s)-5.4(c)-1(r)-5.5(i).1(b)-5.6(e)-1(d)-374.2(a)-6.7(bo)-5.6(ve)-6.7(,)-376.5(a)-1(nd)-379.9(th)-5.6(e)-375.3(r)-5.5(el)-5.7(at)-5.7(ive)-381.1(g).2(e)-6.7(n).2(e)]TJ 0 -1.1174 TD -.0222 Tc [(ex)5.5(pr)5.5(essi)5.4(o)5.5(n)-380.4(of)]TJ /F5 1 Tf 5.5754 0 TD -.0215 Tc [(Tr)6.4(kB)]TJ /F4 1 Tf 1.9007 0 TD 0 Tc (,)Tj /F5 1 Tf .6048 0 TD -.0277 Tc [(R)-6.9(unx)-6.9(2)]TJ /F4 1 Tf 2.4364 0 TD .3605 Tc [(,a)387(n)388.2(d)]TJ /F5 1 Tf 2.3615 0 TD -.0256 Tc [(Oste)-4.8(rix)]TJ /F4 1 Tf 3.1506 0 TD -.024 Tc [(was)-382(a)2.5(ls)3.9(o)-382.2(d)-2.1(et)3.6(ected)-382.2(b)3.7(y)]TJ -16.0293 -1.1116 TD -.0215 Tc [(RT)5(-P)6.4(C)5.2(R)-.6(.)]TJ 1.0137 -1.1116 TD -.016 Tc [(The)-415.7(s).4(eque)-16(n)9.4(c)-1(e)-409.9(o).2(f)-414.5(t).1(he)-415.7(sense)-415.7(a)-1(nd)-408.8(a)-16(n)9.4(tise)-16(n)9.4(se)-409.9(p)-16(r)10.6(imers)-414.3(u).2(se)-16(d)-399.5(t)0(o)]TJ -1.0137 -1.1174 TD -.0153 Tc [(d)-15.3(e)10.1(tect)]TJ /F5 1 Tf 2.6149 0 TD -.0157 Tc (TrkB)Tj /F4 1 Tf 2.2348 0 TD -.0152 Tc [(mRNA)-293.6(wa)-15.2(s)]TJ /F5 1 Tf 4.9188 0 TD [(GGGA)-15.2(C)9.2(A)-.2(CCACGA)-15.2(A)9(CAGAAGT)]TJ /F4 1 Tf 13.1091 0 TD -.0156 Tc (and)Tj /F5 1 Tf -22.8776 -1.1116 TD -.0152 Tc [(G)-15.2(A)9.3(CGCAATC)-15.2(A)9.2(CCACCAC)-15.2(A)9.2(G)]TJ /F4 1 Tf 12.0608 0 TD -.016 Tc [(,)-301.7(r).2(espe)-16(c)8.3(tive)-16(l)9.3(y.)-301.7(The)-300.5(s)-16(e)9.6(quenc)-16(e)-291.2(o).2(f)]TJ -12.0608 -1.1116 TD 0 Tc [(th)26.5(e)-284.5(s)16.4(e)15(n)16.2(se)-268.1(an)25.4(d)-283.3(a)15(n)16.2(t)16.1(i)16.1(s)0(e)25.6(n)16.2(s)16.4(e)-284.5(p)16.2(r)0(i)26.5(m)15(e)15(r)16.2(s)-283.1(f)16.2(or)]TJ /F5 1 Tf 14.0882 0 TD -.0156 Tc (Runx2)Tj /F4 1 Tf 2.7819 0 TD -.0152 Tc [(mRNA)-299.4(wa)-15.2(s)]TJ /F5 1 Tf 4.9245 0 TD 0 Tc [(TG)25.9(G)15.3(T)]TJ -21.7947 -1.1174 TD .0136 Tc [(TAC)-5.8(T)1.1(G)-5.6(T)1.2(CA)-6(TG)-5.6(GC)-5.8(GGG)-5.6(TA)]TJ /F4 1 Tf 11.5309 0 TD -.015 Tc [(an)-15(d)]TJ /F5 1 Tf 1.7567 0 TD -.0155 Tc [(T)-15.5(C)10.2(TCAGAT)-15.5(C)10.2(G)-.2(TTG)-15.5(A)9(A)-.5(CCT)]TJ -13.2876 -1.1116 TD .0183 Tc [(TGCT)5.8(A.)]TJ /F4 1 Tf 3.9051 0 TD -.0156 Tc [(The)-455.6(s).8(eq)-15.6(u)11(e)-.6(nce)-455.6(o)-15.6(f)-444(t).5(he)]TJ /F5 1 Tf 8.8757 0 TD 0 Tc [(Os)25.9(t)16.1(e)15(r)16.4(i)0(x)]TJ /F4 1 Tf 3.3003 0 TD -.0154 Tc [(mRNA)-455.1(pr)-15.4(i)11.1(mers)-459.8(w)-.1(as)]TJ /F5 1 Tf -16.0811 -1.1116 TD 0 Tc [(CC)24.5(T)16.3(C)15.2(T)16.3(G)15.3(CG)24.7(G)15.3(G)15.3(A)15(C)15.2(T)16.3(CA)24.4(A)15(C)15.2(A)15(A)15(C)]TJ /F4 1 Tf 13.1552 0 TD -.015 Tc [(an)-15(d)]TJ /F5 1 Tf 1.9237 0 TD -.0154 Tc [(AGCCCA)-15.4(T)10.2(T).9(AGTG)-15.4(C)9.3(T)1(T)]TJ -15.0789 -1.1174 TD -.0152 Tc [(G)-15.2(T)10.7(AAAGG.)-335.4(GAPDH)]TJ /F4 1 Tf 8.6568 0 TD -.0158 Tc [(w)-15.8(a)8.8(s)-333.5(u).4(se)-15.8(d)-324.4(a)-.8(s)-333.5(a)-334.8(refe)-15.8(r)9.7(e)-.8(nce)-334.8(g).4(e)-15.8(n)9.6(e.)]TJ -7.6431 -1.1116 TD 0 Tc [(Total)-532.3(protein)-533.2(was)-529.3(extracted)-533.2(and)-528.6(subjected)-537.6(to)-526.5(Western)]TJ -1.0137 -1.1116 TD [(blotting.)-421.7(Transfected)-421(cells)-422.6(collected)-423.9(at)-418.2(0)]TJ /F10 1 Tf 16.9163 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C)-416.8(i)0(n)-417(sodium)-416.7(do-)]TJ -17.3137 -1.1116 TD [(decyl)-382.3(sulfate)-384.4(\(SDS\))-374.6(lysis)-379.8(buffer)-382.1(\(Beyotime)-383.4(Biotechnology,)]TJ 0 -1.1174 TD [(China\))-440.9(were)-439.5(further)-435.1(lysed)-438.6(by)-434.2(supersonic)-439.3(on)-434.2(ice)-437.7(for)-435.2(2)-168.1(min)]TJ 0 -1.1116 TD [(discontinuously.)-499.3(Supernatants)-500.4(were)-491.4(collected)-498.8(after)-497.5(centri-)]TJ T* [(fuge)-316.6(for)-308.5(15)-169.2(min)-309.9(at)-308.8(4)]TJ /F10 1 Tf 8.15 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C,)-310.8(12,000)]TJ /F5 1 Tf 4.2852 0 TD (g)Tj /F4 1 Tf .5011 0 TD [(.)-308.7(After)-312.9(being)-312.1(denatured)-313(for)]TJ -13.3337 -1.1174 TD [(5)-168.1(min)-390.6(at)-389.4(100)-383.4(with)-391.4(loading)-389.3(buffer)-387.8(\(Huaxingbio)-8.6(,)-383.6(China\))-389(and)]TJ 0 -1.1116 TD [(were)-341.6(quantied)-346.4(by)-336.3(the)-338.7(BCA)-346.1(Protein)-337.2(Assay)-341.2(\(Pierce\),)-343.9(a)-342.1(total)]TJ T* [(of)-330.5(20)]TJ /F6 1 Tf 2.3327 0 TD (m)Tj /F4 1 Tf .5529 0 TD [(g)-323.6(protein/lane)-334(was)-333.4(used)-327.9(for)-331.5(SDS/polyacrylamide)-332(gel)]TJ -2.8856 -1.1174 TD [(electrophoresis)-343.7(\(SDS-PAGE\).)]TJ 1.0137 -1.1116 TD [(Each)-370.8(sample)-373(was)-373.8(run)-371.9(on)-370.8(a)-370.9(10%)-367.2(polyacrylamide)-378.8(gel)-367.5(and)]TJ -1.0137 -1.1116 TD [(transferred)-435.9(to)-434.3(a)-428.5(polyvinylidene)-433(uoride)-435(membrane)-435.2(\()-81.7(Milli-)]TJ T* [(pore\).)-453.5(The)-449.2(membranes)-453.4(were)-451.1(incubated)-457.2(in)-445.8(blocking)-453.7(buffer)]TJ 0 -1.1174 TD [(\(5%)-332.6(skimmed)-333.8(milk)-328.4(in)-330.6(Tris-buffered)-334.4(saline)-337.3(containing)-330.5(0.1%)]TJ 0 -1.1116 TD [(Tween-20\))-273.4(for)-262.4(1)-168.1(h)-266(and)-263.6(incubated)-272.9(with)-264.7(the)-269.5(following)-264.6(primary)]TJ T* [(antibodies)-549.2(at)-544.9(4)]TJ /F10 1 Tf 6.4451 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C)-543.5(overnight:)-548.2(TrkB)-548(\(1:1000,)-541.1(#4603;)-548.2(Cell)]TJ -6.8425 -1.1174 TD [(Signaling)-477.8(Technology\),)-480(Erk1/2)-480.2(\(1:1000,)-472(#4695;)-479(Cell)-473.4(Sig-)]TJ 0 -1.1116 TD [(naling)-428.5(Technology\),)-433.9(phospho-Erk1/2)-425.4(\(1:1000,)-431.7(#4370;)-427.2(Cell)]TJ T* [(Signaling)-460.6(Technology\),)-462.7(Runx2)-461.6(\(1:500,)-453.6(abs116236;)-461.4(Absin,)]TJ 0 -1.1174 TD [(China\),)-513.4(Osterix)-505.1(\(1:300,)-511.2(abs120764;)-507.5(Absin\),)-506.2(and)-511.3(GAPDH)]TJ 0 -1.1116 TD [(\(1:1000,)-587.2(TA-08;)-579(ZSGB-Bio,)-586.5(China\).)-582.6(Based)-590.4(on)-578.2(the)-580.6(host)]TJ T* [(species)-327.7(of)-318.9(primary)-327(antibody,)-318.9(HRP-conjugated)-326.2(anti-rabbit)-325.9(or)]TJ 0 -1.1174 TD [(anti-mouse)-596.3(IgG)-591.6(\(ZSGB-Bio\))-591(was)-592.6(used)-592.9(for)-590.7(1)-168.1(h)-588.6(at)-591(room)]TJ 0 -1.1116 TD [(temperature,)-349.9(The)-345.5(bands)-340.5(were)-347.4(detected)-347.8(with)-339.6(the)-344.4(chemilumi-)]TJ T* [(nescence)-452.2(methodology)-452.5(\(ECL)-445.5(Plus;)-448.9(Solarbio\))-448.9(by)-445.7(a)-445.8(lumino)]TJ T* [(imaging)-338.7(analyzer)-336.1(\(VILBER)-335.5(Fusion)-334.7(FX5,)-335.8(France\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 59.7543 138.7842 Tm [(p75)-335.7(and)-335.7(s100)-328.9(staining)-337.1(of)-330.4(hBMSCs)-339.3(treated)-330.4(with)-336.5(BDNF)]TJ /F4 1 Tf 9.843 0 0 9.843 69.7323 122.3433 Tm 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[(assessed)-535.6(using)-535.3(an)-533.3(Olympus)-533.9(IX71)-535.1(microscope)-534(\(Olympus,)]TJ 0 -1.1174 TD [(Tokyo,)-332.7(Japan\).)]TJ /F2 1 Tf 8.9663 0 0 8.9663 310.8472 538.8093 Tm [(In)-330.4(vivo)]TJ /F11 1 Tf 3.2689 0 TD (experiments)Tj /F4 1 Tf 9.843 0 0 9.843 320.8251 522.3683 Tm [(Six-week-old)-506(male)-503.4(BALB/c)-507.4(homozygous)-508.6(nude)-500.9(\(nu/nu\))]TJ -1.0137 -1.1116 TD [(mice)-324.9(were)-330.1(purchased)-324.2(from)-328.1(Peking)-324.5(University)-330(Experimental)]TJ 0 -1.1174 TD [(Animal)-390.3(C)-25.2(e)-19.5(n)-18.4(t)-24.3(e)-19.5(r)-18.3(,)-412.4(B)-25.2(e)-19.5(i)-18.5(j)-24.3(i)-18.5(n)-18.4(g)-24.1(,)-406.6(C)-25.2(h)-18.4(i)-18.5(n)-24.1(a)-19.5(.)-412.4(A)-19.2(n)-24.1(i)-18.5(m)-19.6(a)-19.5(l)-24.3(s)-409.8(w)-19.2(e)-25.3(r)-18.3(e)-411.2(a)-25.3(l)-18.5(l)-18.5(o)-24.1(w)-19.2(e)-19.5(d)-410(a)]TJ 0 -1.1116 TD [(wee)10.8(k)-358.2(t)0(o)-359.4(acc)10.5(lim)12.5(ati)12.6(ze)-355.9(to)-359.4(the)-355.9(hou)14(sin)14(g)-364(e)0(n)13.9(vir)13.9(onm)12.7(ent)-355.9(bef)12.8(ore)-355.8(ex)13.9(-)]TJ T* [(per)12.9(im)13.7(ent)12.7(ati)12.6(on.)-247.5(hB)14(MSC)12.2(s)-254.3(wer)12(e)-255.7(cul)12.7(tur)13.9(ed)-245.3(for)-245.1(7)-254.5(day)12.8(s)-254.3(i)0(n)-250(dif)13.9(fer)12.9(en)13.9(t)]TJ 0 -1.1174 TD [(me)12.7(dia)12.7(,)-400.8(acc)16.2(ord)14(ing)-389.3(to)-394(the)-384.7(exp)12.8(eri)12.7(men)11.6(tal)-384.9(des)13(ign)-389.3(\(ex)12.8(per)12.8(ime)11.5(nta)18.4(l)]TJ 0 -1.1116 TD [(gro)14(ups)-440.8(wer)12(e)-451.5(\(I\))]TJ /F6 1 Tf 6.975 0 TD (b)Tj /F4 1 Tf .5472 0 TD [(-T)13.9(CP,)-444.2(\(II)14.1(\))]TJ /F6 1 Tf 4.6193 0 TD (b)Tj /F4 1 Tf .5472 0 TD [(-T)13.9(CP)]TJ /F10 1 Tf 2.1426 0 TD (+)Tj /F4 1 Tf .5472 0 TD [(CM-)12.1(tre)12.7(ate)11.5(d)-450.4(hBM)12(SCs)13.3(,)]TJ -15.3784 -1.1116 TD [(\(II)14.1(I\))]TJ /F6 1 Tf 1.8892 0 TD (b)Tj /F4 1 Tf .5472 0 TD [(-TC)11.8(P)]TJ /F10 1 Tf 2.1484 0 TD (+)Tj /F4 1 Tf .5472 0 TD [(OM)13.3(-tr)13.9(eat)11.5(ed)-239.5(hBMSCs,)-248.8(and)-252.1(\(IV\))]TJ /F6 1 Tf 12.6886 0 TD (b)Tj /F4 1 Tf .5529 0 TD (-TCP)Tj /F10 1 Tf 2.4191 0 TD (+)Tj /F4 1 Tf .5472 0 TD [(100)-170.3(ng/)]TJ -21.3397 -1.1116 TD [(mL)-350.2(BDNF)]TJ /F10 1 Tf 4.4004 0 TD (+)Tj /F4 1 Tf .5529 0 TD [(OM-treated)-356.3(hBMSCs\).)]TJ /F6 1 Tf 9.6187 0 TD (b)Tj /F4 1 Tf .5529 0 TD [(-tri-calcium)-358.2(phosphate)]TJ -15.125 -1.1174 TD [(particles)-531.9(\()]TJ /F6 1 Tf 4.2679 0 TD (b)Tj /F4 1 Tf .5529 0 TD [(-TCP,)-534(50500)]TJ /F6 1 Tf 6.1168 0 TD (m)Tj /F4 1 Tf .5529 0 TD [(m;)-527.7(Bicon,)-535.4(Boston,)-529.4(MA\))-534.9(were)]TJ -11.4906 -1.1116 TD [(incubated)-255.6(with)-259(each)-255.6(CM)-257.6(at)-256.9(37)]TJ /F10 1 Tf 12.0839 0 TD ()Tj /F4 1 Tf .3974 0 TD [(C)-255.6(for)-256.7(1)-162.4(h)-254.5(to)-255.8(aid)-258(cell)-254.7(adhesion.)]TJ -12.4813 -1.1116 TD [(hBMSCs)-285.7(from)-287.8(group)-281.9(II,)-287.8(III,)-283.1(and)-286.7(VI)-285.3(where)-285.1(then)-287.9(resuspended)]TJ 0 -1.1174 TD [(and)-332.8(seeded)-338.2(onto)-332.8(the)]TJ /F6 1 Tf 8.5186 0 TD (b)Tj /F4 1 Tf .5529 0 TD [(-TCP)-334.7(particles.)]TJ -8.0578 -1.1116 TD [(During)-387.7(the)]TJ /F5 1 Tf 4.8382 0 TD [(in)-388.2(vivo)]TJ /F4 1 Tf 3.237 0 TD [(experiments,)-394.7(mice)-394(were)-387.7(anesthetized)]TJ -9.0888 -1.1116 TD [(with)-374.2(sodium)-370.6(pentobarbital)-381.2(and)-373.1(four)-373(enclosed)-375.1(subcutaneous)]TJ 0 -1.1174 TD [(transplantation)-348.7(cavities)-352.3(created)-346.5(in)-347.9(the)-344.4(dorsal)-347.5(area)-347.7(using)-345.3(he-)]TJ 0 -1.1116 TD [(mostatic)-398.5(forceps.)]TJ /F6 1 Tf 7.3897 0 TD (b)Tj /F4 1 Tf .5529 0 TD [(-TCP)-398.1(complexes)-400.5(from)-391.5(each)-399.6(of)-393.8(the)-396.3(four)]TJ -7.9426 -1.1116 TD [(groups)-737.9(were)-739.1(transplanted)-742.6(into)-736.1(individual)-738.4(subcutaneous)]TJ 0 -1.1174 TD [(cavities)-335(\()]TJ /F5 1 Tf 3.738 0 TD (n)Tj /F10 1 Tf .6681 0 TD (=)Tj /F4 1 Tf .72 0 TD [(6)-335.2(per)-332.7(group)-333.8(at)-337.6(each)-336.2(time)-335.4(point\).)-338.6(After)-335.9(surgery,)]TJ -5.1261 -1.1116 TD [(animals)-391.5(were)-393.5(carefully)-388(monitored)-392.7(two)-390.2(times)-393.9(a)-388.2(day)-390.4(and)-390.4(no)]TJ T* [(adverse)-477.5(effects)-483.4(due)-482.5(to)-474.6(the)-482.7(surgery)-475.2(were)-485.6(observed)-477.5(in)-480.4(any)]TJ T* [(individual.)-327.2(Animals)-327.8(were)-330.1(sacriced)-331.1(at)-326(4)-329.4(and)-327(8)-323.6(weeks)-331.1(using)]TJ 0 -1.1174 TD (CO)Tj 7.3823 0 0 6.5614 324.4535 279.6094 Tm (2)Tj 9.843 0 0 9.843 331.9369 281.2535 Tm [(asphyxiation)-378.6(and)-384.6(samples)-379.6(from)-385.7(each)-382.3(group)-379.9(were)-382(har-)]TJ -2.1426 -1.1116 TD [(vested)-331.4(and)-327(immediately)-335.4(xed)-327.9(in)-330.6(4%)-325.8(paraformaldehyde.)-339.2(All)]TJ T* [(animal)-430.9(studies)-429.2(were)-433.8(performed)-428.1(in)-428.5(accordance)-438.4(with)-426(proce-)]TJ 0 -1.1174 TD [(dures)-352(approved)-356.7(by)-353.5(the)-355.9(Animal)-355.7(Care)-359.1(and)-355.8(Ethics)-354.6(Committee)]TJ 0 -1.1116 TD [(of)-330.5(Peking)-336(University)-335.8(Health)-338.4(Science)-334.9(Center)-338.4(\(LA2015158\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 310.8472 215.4897 Tm [(Histological)-333.4(study)]TJ /F4 1 Tf 9.843 0 0 9.843 320.8251 199.0488 Tm [(Specimens)-417.6(were)-422.3(decalcied)-425.9(for)-417.9(14)-422.7(days)-420.1(in)-417(10%)-419.1(EDTA)]TJ -1.0137 -1.1174 TD [(\(pH)-349.7(7.4\).)-350(After)-347.4(decalcication,)-360.3(specimens)-348.4(were)-353.2(dehydrated)]TJ 0 -1.1116 TD [(and)-557.4(embedded)-566.5(in)-555.3(parafn)-562.7(wax.)-561.7(Next,)-562.9(5-)]TJ /F6 1 Tf 17.7745 0 TD (m)Tj /F4 1 Tf .5472 0 TD [(m-thick)-563.3(tissue)]TJ -18.3216 -1.1116 TD [(sections)-448.7(were)-451.1(stained)-447.8(with)-449(hematoxylin)-448(and)-448(eosin)-444.3(\(H&E\))]TJ T* [(and)-315.5(Massons)-321.3(trichrome)-318.9(stains.)-316.3(Osteogenesis)-322.5(was)-316.2(evaluated)]TJ 0 -1.1174 TD [(by)-439.9(immunohistochemical)-450.2(staining)-447.9(using)-443.2(1:200)-443.4(osteocalcin)]TJ 0 -1.1116 TD [(\(OCN\))-330.8(antibody)-327(\(sc-30044;)-334.6(Santa)-324.6(Cruz\).)-333.6(Neurogenesis)-334.1(was)]TJ T* [(evaluated)-579.3(by)-578.2(immunohistochemical)-582.7(staining)-580.4(using)-575.6(1:200)]TJ 0 -1.1174 TD [(microtubule-associated)-349.4(protein)-348.9(2)-340.9(\()-87.5(MAP2\))-341.2(\(sc-20172;)-346.1(Santa)]TJ 0 -1.1116 TD [(Cruz\),)-235.7(1:200)-236(glial)-243.2(brillary)-235.9(acidic)-240.7(protein)-239.5(\(GFAP\))-238.4(\(ab33922;)]TJ T* [(Abcam\),)-555.9(1:500)-552.8(neural/glial)-558.7(antigen)-557.5(2)-554(\(NG2\))-554.4(\(ab139406;)]TJ 0 -1.1174 TD [(Abcam\),)-388.8(and)-390.4(1:1000)]TJ /F6 1 Tf 8.8699 0 TD (b)Tj /F4 1 Tf .5529 0 TD [(-tubulin)-389.3(III)-389.1(\(ab78078;)-391.3(Abcam\))-391.1(anti-)]TJ -9.4229 -1.1116 TD [(bodies.)-506.5(Three)-504.3(elds)-507.5(from)-506.7(three)-509(slides)-508.7(from)-506.7(each)-503.2(sampl)-7.8(e)]TJ T* [(were)-272.5(used)-270.3(to)-273(semiquantitatively)-279.9(assess)-273.1(the)-269.5(optical)-275.4(density)-273.9(of)]TJ /F8 1 Tf 8.9663 0 0 8.9663 59.7543 749.7069 Tm [(EFFECT)-338(OF)-337.5(BDNF)-330.2(ON)-334.6(BONE)-335.4(NEUROGENESIS/OSTEOGENESIS)-22070.5(1285)]TJ ET endstream endobj 52 0 obj <>stream /GS1 gs BT /F4 1 Tf 9.843 0 0 9.843 62.022 523.5022 Tm 0 0 0 rg 0 Tc 0 Tw [(positive)-361.5(staining)-361.5(\(integrated)-361.5(optical)-361.8(density/tissu)-9.8(e)-359.4(area\))-360.3(us-)]TJ 0 -1.1116 TD [(ing)-395.1(Image)-400.7(Pro)-394.8(Plus)-395.8(\()-81.7(Media)-400.5(Cybernetics;)-403.8(Roper)-393.6(Technolo-)]TJ T* [(gies,)-337.2(Lakewood)-335.8(Ranch,)-334.8(FL\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 62.022 478.6014 Tm [(Statistical)-336.1(analysis)]TJ /F4 1 Tf 9.843 0 0 9.843 72 462.1605 Tm [(Da)24.6(ta)-493.1(w)15.3(e)0(r)19.7(e)-497.6(an)19.7(a)15(l)0(y)20.7(z)0(e)24.3(d)-502.2(us)21(i)16.1(n)0(g)-491.8(S)16.3(PS)21.2(S)-502(s)16.4(of)20.9(tw)25.6(ar)19.7(e)-497.6(\()0(S)21(P)0(S)21.2(S)16.3(;)-502.3(I)0(B)19.8(M)15.3(,)]TJ -1.0137 -1.1174 TD [(Ar)20(m)15(o)0(n)20.8(k)16.2(,)-493(N)0(Y)24.9(\))-496.4(a)15(n)0(d)-480.3(s)0(t)20.9(a)15(ti)20.6(st)26.7(ic)19.6(al)-481.5(s)16.4(i)0(g)20.7(n)0(i)26.5()0(c)19.8(a)0(n)25.4(c)0(e)-482.6(w)0(a)24.6(s)-496.2(a)15(s)0(s)21.2(e)0(s)25.6(s)0(e)19.9(d)-490.7(by)]TJ 0 -1.1116 TD -.0186 Tc [(o)-18.6(n)2.2(e-)-18.6(wa)-18.6(y)-235.1(a)-18.6(nal)-18.6(y)2.1(s)-18.6(i)8.1(s)-249.9(o)-18.6(f)-233.9(v)-18.6(ar)-18.6(i)7.9(a)-18.6(nc)-18.6(e)-236.2(a)-18.6(nd)]TJ /F5 1 Tf 13.2358 0 TD 0 Tc (t)Tj /F4 1 Tf .2707 0 TD [(-t)26.5(es)19.9(ts)-215.2(\(n)20.9(on)26.6(pa)19.7(ra)25.5(me)18.4(t)16.1(r)0(i)20.7(c)-226.9(te)19.6(st)20.9(s)16.4(\))0(.)]TJ /F5 1 Tf -13.5065 -1.1116 TD [(Po)25.4(st)-445.6(ho)20.8(c)]TJ /F4 1 Tf 4.0836 0 TD [(te)25.3(st)20.9(in)20.7(g)-456.1(f)16.2(or)-445.7(mu)19.6(l)16.1(t)0(i)20.6(p)0(l)26.5(e)-463(c)15(o)0(m)19.6(p)16.2(ar)19.7(is)26.7(on)20.8(s)-455.9(w)0(a)18.8(s)-455.9(c)15(a)0(r)19.7(r)0(i)26.5(e)0(d)-446.9(o)0(u)20.8(t)]TJ -4.0836 -1.1174 TD [(us)21(i)16.1(n)0(g)-359.3(a)-370.9(Fi)26.6(sh)21(er)25.5(s)-359.1(le)19.6(a)15(s)0(t)-359.2(s)0(i)20.9(g)16.2(ni)20.7(c)25.6(an)19.7(t)-369.8(d)0(i)26.5(f)0(f)20.9(e)0(r)25.5(e)0(n)19.7(c)0(e)-355.9(t)0(e)19.6(s)0(t)26.7(.)-372(W)13.9(h)0(e)19.7(n)-369.7(v)16.2(a)0(r)19.7(i)0(-)]TJ 0 -1.1116 TD [(an)19.7(c)15(e)-313.3(wa)18.8(s)-311.9(n)0(o)20.8(t)-312.2(ho)26.6(mo)19.6(g)16.2(e)0(n)19.7(e)0(o)25.4(u)0(s)21(,)-314.5(a)-313.3(K)0(r)20(u)16.2(sk)21(al)25.3(W)18.6(a)15(l)0(l)20.6(i)0(s)-301.6(t)0(e)25.3(s)0(t)-301.6(w)0(a)18.8(s)-311.9(us)21(e)15(d)0(,)]TJ T* [(fo)20.9(l)16.1(l)0(o)20.7(w)0(e)24.6(d)-277.6(b)16.2(y)-277.6(a)-273(N)0(e)18.8(m)15(en)19.7(y)16.2(i)-277.7(te)25.3(st)-267.1(f)16.2(o)0(r)-267.1(m)15(ul)20.7(t)16.1(i)0(p)20.7(l)0(e)-262.7(c)0(o)19.7(m)15(pa)19.7(r)16.2(i)0(s)20.9(o)0(n)26.6(s)0(.)-263.5(F)0(o)21(r)-271.8(al)19.5(l)]TJ T* [(te)19.5(s)16.4(t)0(s)20.9(,)-320.2(th)20.7(e)-319(t)0(h)20.7(r)16.2(es)19.9(ho)20.8(l)16.1(d)-323.6(fo)26.6(r)-323.6(s)0(t)20.9(a)15(ti)20.6(st)26.7(ic)19.6(al)-308.8(si)20.9(gn)26.6(i)20.9(c)15(a)0(n)19.7(c)0(e)-309.8(w)0(a)18.8(s)]TJ /F5 1 Tf 20.0841 0 TD (p)Tj /F10 1 Tf .6566 0 TD (<)Tj /F4 1 Tf .7084 0 TD -.0162 Tc [(0.)-16.2(0)8.1(5)-16.2(.)]TJ /F8 1 Tf 8.9663 0 0 8.9663 62.022 360.3968 Tm 0 Tc (Results)Tj /F11 1 Tf 0 -1.8273 TD [(Cell)-336.3(proliferation)-338.6(and)-329.4(osteogenic)-335.9(differentiation)]TJ 0 -1.2266 TD [(of)-336.7(hBMSCs)]TJ /F4 1 Tf 9.843 0 0 9.843 72 316.5731 Tm [(The)-247.6(assessment)-257(of)-244.1(cell)-254.7(proliferation)-247.5(showed)-250.4(that)-253.5(hBMSCs)]TJ -1.0137 -1.1116 TD [(proliferated)-483.5(over)-477.8(time)-479.4(and)-482.5(that)-478.1(BDNF)-479.3(did)-475.7(not)-481.5(show)-477.4(any)]TJ 25.504 22.1345 TD [(effect)-373(on)-370.8(proliferation.)-371.8(There)-371.9(was)-373.8(no)-365.1(signicant)-376.2(difference)]TJ 0 -1.1116 TD [(betwe)-8.8(en)-504.5(the)-511.4(control)-504.4(group)-512.3(and)-505.6(the)-511.4(BDNF-treated)-509.1(group,)]TJ T* [(regardless)-394.3(of)-388.1(the)-384.7(concentration)-393.7(of)-388.1(added)-388(BDNF)-387.2(\(Fig.)-387.9(1A\).)]TJ 0 -1.1174 TD [(Howev)-8.4(er,)-317.8(100)-164.6(ng/mL)-319.1(BDNF)-318(did)-320.2(signicantly)-321(promote)-321.2(ALP)]TJ 0 -1.1116 TD [(activity)-270.8(in)-267.3(hBMSCs)-274.2(when)-265.6(compared)-272.7(to)-267.3(cells)-267.1(cultured)-270.5(in)-267.3(OM)]TJ T* [(only)-505.6(\()]TJ /F5 1 Tf 2.7877 0 TD (p)Tj /F10 1 Tf .6681 0 TD (=)Tj /F4 1 Tf .72 0 TD [(0.037\).)-501.9(This)-506.6(was)-512(slightly)-504.5(higher)-509(than)-501(the)-511.4(ALP)]TJ -4.1758 -1.1174 TD [(activity)-443.6(observed)-437.1(in)-434.3(the)-436.6(50)-169.2(ng/mL)-434.3(BDNF)-439(group,)-435.1(although)]TJ 0 -1.1116 TD [(there)-416.9(was)-414.1(no)-416.9(statistical)-419.2(difference.)-416.5(OM)-412.9(was)-414.1(also)-414.4(found)-414.4(to)]TJ T* [(promote)-321.2(osteogenic)-319.8(differentiation)-320.1(by)-319(hBMSC)-313.6(compared)-318.8(to)]TJ 0 -1.1174 TD [(the)-350.2(control)-354.7(medium)-350.2(\(Fig.)-347.6(1B\).)-347.6(An)-348.7(analysis)-350.8(of)-347.7(gene)-352.3(expres-)]TJ 0 -1.1116 TD [(sion)-505.4(indicated)-503.4(that)-501.2(BDNF)-508.1(signicantly)-505.3(increased)-504(the)-499.9(ex-)]TJ T* [(pression)-320.7(of)]TJ /F5 1 Tf 4.8036 0 TD (ALP)Tj /F4 1 Tf 2.0965 0 TD [(mRNA)-313.7(compared)-318.8(to)-319.1(cells)-318.9(grown)-317.4(in)-313.4(CM)-315.2(or)]TJ -6.9001 -1.1116 TD [(OM)-522.4(only)-522.9(without)-521.6(BDNF)-525.4(\()]TJ /F5 1 Tf 11.6922 0 TD (p)Tj /F10 1 Tf .6624 0 TD (<)Tj /F4 1 Tf .72 0 TD [(0.05\))-520.4(\(Fig.)-526.1(2A\).)-520.2(This)-518.2(was)]TJ -13.0745 -1.1174 TD [(supported)-431.4(by)-422.7(the)-425(ALP)-425.7(activity)-426.4(assay.)-425.6(Finally,)-427.2(alizarin)-427.4(red)]TJ 0 -1.1116 TD [(staini)-8(ng)-238.3(demonstrated)-242.6(that)-242(BDNF)-243.2(promoted)-241.7(the)-235(formation)-242.9(of)]TJ T* [(the)-528.7(mineralized)-536.7(extracellular)-533.2(matrix)-527.6(\(ECM\))-532.7(by)-526.3(hBMSCs)]TJ 0 -1.1174 TD [(after)-307.4(14)-295.9(days,)-302.6(when)-300.2(compared)-301.5(to)-301.8(cells)-301.6(grown)-300.1(in)-296.1(CM)-303.6(or)-295.9(OM)]TJ 0 -1.1116 TD [(only)-338.6(\(Fig.)-330.3(2B\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 313.0582 311.981 Tm [(BDNF)-338(promoted)-332.9(BMSC)-335.4(osteogenesis)-333.5(via)]TJ 0 -1.2266 TD [(the)-334.8(Erk/Runx2/Osterix)-334.8(pathway)]TJ /F4 1 Tf 9.843 0 0 9.843 323.0361 284.5416 Tm [(To)-412.3(clear)-14.9(ly)-411.3(deter)-13.7(mine)-415.9(the)-419.3(signal)-7.8(i)-7(n)0(g)-411.1(pathw)-13.4(ay)-412.3(resp)-11.1(onsible)]TJ -1.0137 -1.1116 TD [(f)-6.8(o)0(r)-486(the)-494.2(osteog)-7.7(enes)-12.3(is)-486(pro)-9(motin)-7(g)-484.9(eff)-10.2(ect)-489.6(of)-491.7(BDNF,)-494.3(BMSCs)]TJ T* [(w)-7.7(ere)-293.6(tr)-8.1(ansfec)-9.9(ted)-298.3(with)-299.3(siRNA-)-9.3(Tr)-9.1(kB,)-294.7(treate)-10.3(d)-294.8(with)-299.3(100)-170.3(ng/mL)]TJ 0 -1.1174 TD [(B)-7.9(DNF,)-590(and)-586.2(then)-593.2(cultiv)-8.2(ated)-594.3(for)-585(48)-169.2(h)-588.6(t)0(o)-584.1(knockd)-13.5(own)-585.9(the)]TJ 0 -1.1116 TD [(B)-7.9(DNF)-338.9(rec)-11.4(eptor)-340.8(g)-6.9(ene.)-343.1(In)-342(additi)-8.2(on,)-345.5(an)-337.4(siRN)-12(A)-336(was)-345(also)-345.3(used)]TJ T* [(a)-8(s)-444.4(negat)-8(ive)-448.1(con)-10.2(trol.)-451.6(RT-PC)-8.6(R)-445.6(resul)-12.3(ts)-445.6(showed)-452(th)-8.1(at)-447(siRNA-)]TJ T* [(Tr)-9.1(kB)-412.2(knocke)-8.9(d)-410(d)0(o)-8(w)0(n)-412(more)-415.7(than)-414.6(90)-8(%)-411.1(o)0(f)-411.1(the)-413.5(orig)-10.3(inal)]TJ /F5 1 Tf 22.2901 0 TD (TrkB)Tj /F4 1 Tf -22.2901 -1.1174 TD [(ge)13.9(ne)19.7(.)-377.8(T)0(h)19.6(e)-376.6(ex)19.7(pr)15.1(es)19.9(si)20.9(on)-370.8(le)19.6(ve)19.7(ls)-365(of)-370.8(os)21(te)19.6(og)15.1(en)19.7(ic)-366.3(tr)20.7(an)13.9(sc)19.9(ri)20.7(pt)20.7(io)20.7(n)-381.2(f)0(a)19.7(c)0(-)]TJ 0 -1.1116 TD [(to)15(rs)]TJ /F5 1 Tf 1.6991 0 TD (Runx2)Tj /F4 1 Tf 2.7877 0 TD (and)Tj /F5 1 Tf 1.6818 0 TD (Osterix)Tj /F4 1 Tf 3.1736 0 TD [(were)-232.2(all)-229.4(markedly)-231.3(reduced)-230(in)-232.7(siRNA-)]TJ -9.3422 -1.1116 TD [(TrkB)-242.7(knockdown)-236.6(group)-241.6(compared)-238.1(with)-241.7(those)-242.8(in)-238.5(the)-246.5(negative)]TJ 0 -1.1174 TD [(control)-504.4(group)-506.6(\(Fig.)-503.1(3AC\).)-506.2(This)-500.9(result)-508.9(indicated)-503.4(that)-501.2(by)]TJ 0 -1.1116 TD .0235 Tc [(bi)5(n)5.1(d)-.6(i)5(n)5.1(g)-409.6(w)4.3(it)5(h)-409.6(T)3.9(r)5.2(k)5.1(B,)-406.1(BDNF)-403.6(pl)5(ay)5.1(ed)-403.8(a)-410.7(p)5.1(os)5.3(i)5(t)-.8(i)5(v)5.1(e)-410.7(r)5.2(ol)5(e)-405(i)-.8(n)-403.8(o)-.6(s)5.3(-)]TJ T* 0 Tc [(teoge)-8(nic)-373.2(differe)-10.1(ntiati)-8.3(on)-370.8(of)-370.8(BMSCs)-8.1(.)-366.3(Weste)-10(rn)-370.8(blotti)-7.1(ng)-370.8(assay)]TJ 0 -1.1174 TD [(f)-6.8(urther)-485.9(conrm)-8.8(ed)-481.4(and)-482.5(explor)-7.9(ed)-481.4(this)-488.3(pathwa)-9.9(y,)-482.6(and)-482.5(it)-480.5(was)]TJ 0 -1.1116 TD [(obs)-8.9(erved)-468.6(that)-472.4(the)-465.4(expres)-8.7(si)-7.9(on)-463(level)-474.6(of)-462.9(phosph)-6.4(o-)-7.9(Erk1/2)-468.7(to-)]TJ T* [(gethe)-8(r)-433(with)-437.5(Runx2)-438.5(and)-436.4(Osterix)-441.8(evide)-8(ntly)-436.6(decre)-9(ased)-438.5(when)]TJ 0 -1.1174 TD (the)Tj /F5 1 Tf 1.5666 0 TD (TrkB)Tj /F4 1 Tf 2.3384 0 TD [(gene)-340.8(was)-339.2(knocked)-338.3(down)-339.3(\(Fig.)-341.8(3D\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 313.0582 83.9622 Tm [(Neurogenic)-337.8(potential)-332.9(of)-336.7(hBMSCs)]TJ /F4 1 Tf 9.843 0 0 9.843 323.0361 67.5212 Tm [(Analysis)-292.9(of)-284.4(neurogenesi)-9.8(s)-283.1(after)-290.1(BDNF)-295(treatment)-291.5(indicated)]TJ -1.0137 -1.1116 TD [(that)-247.7(100)-164.6(ng/mL)-244.2(BDNF)-243.2(stimulated)-245.3(hBMSCs)-239.6(to)-244.2(generate)-243.9(more)]TJ ET q 1 i 138.841 732.245 m 475.37 732.245 l 475.37 607.181 l 138.841 607.181 l W n q 336.928 0 0 125.065 138.841 607.181 cm /Im1 Do Q Q BT /F7 1 Tf 9.845 0 0 9.845 62.022 590.3998 Tm [(FIG.)-250.4(1.)]TJ /F4 1 Tf 4.031 0 TD [(Effect)-257.2(of)-249.6(BDNF)-254(on)-249.6(cell)-254.3(proliferation)-252(and)-251.8(ALP)-252.4(activity.)]TJ /F7 1 Tf 22.2913 0 TD (\(A\))Tj /F4 1 Tf 1.6354 0 TD [(Cell)-254.1(proliferation)-257.8(of)-249.6(hBMSCs)-250.3(assessed)-258.4(using)-252.6(a)-249.8(CCK-8)]TJ -27.9577 -1.0135 TD [(assay)-306.4(at)-302.8(day)-297.8(1,)-303.8(3,)-303.8(5,)-298(and)-303.6(7.)-303.8(There)-302.1(were)-306.6(no)-301.4(signicant)-300.3(differences)-309.3(between)-305.1(cells)-301.2(treated)-304.5(with)-304.6(50)-301.4(and)-303.6(100)-164.2(ng/mL)-306.9(BDNF,)-303.5(nor)]TJ T* [(be)19.9(t)16.1(w)0(e)19.1(e)15.1(n)-271.6(C)0(M)-262.9(a)0(n)25.6(d)-271.6(BD)19.2(NF)26.2(,)-274(f)0(r)21(o)16.3(m)-272.8(d)0(a)19.9(y)16.3(s)-271.5(1)-271.6(to)-261.3(7)-271.6(\()]TJ /F5 1 Tf 17.506 0 TD (p)Tj /F10 1 Tf .6565 0 TD (>)Tj /F4 1 Tf .7025 0 TD [(0.)24.4(05)21.1(\).)]TJ /F7 1 Tf 2.5453 0 TD [(\(B)20.1(\))]TJ /F4 1 Tf 1.5836 0 TD [(A)15.5(L)0(P)-262.1(a)0(c)18.7(t)16.1(iv)20.9(it)26.5(y)-271.6(a)0(t)-262.5(d)0(a)25.6(y)-271.6(7)-271.6(a)0(f)19.9(t)0(e)25.5(r)-271.6(st)21(im)25.5(ul)20.9(at)25.5(io)20.9(n)-271.6(b)0(y)-261.1(B)15.3(DN)19.4(F.)-257.6(AL)24.8(P)-271.5(a)0(c)18.7(t)0(i)26.5(v)0(i)20.9(t)0(y)-261.3(w)15.4(as)]TJ -22.9939 -1.0135 TD [(si)21(g)16.3(n)0(i)20.9()0(c)25.8(a)0(n)19.9(t)0(l)26.5(y)-392.6(hi)20.9(g)16.3(h)0(e)19.9(r)-392.6(i)16.1(n)-392.6(ce)18.7(l)16.1(l)0(s)-382.1(t)0(r)20.9(e)15.1(at)19.7(e)15.1(d)-392.6(wi)20.1(t)16.1(h)-392.6(10)21.1(0)-150.7(n)0(g)21.1(/)0(m)25.5(L)-393.7(BD)25(NF)-382.7(co)25.6(mp)19.9(a)15.1(r)0(e)19.9(d)-392.6(t)16.1(o)-392.6(th)20.9(e)-388(o)0(t)20.9(h)0(e)25.6(r)-392.6(gr)21.1(ou)26.8(ps)-381.9(\(*)]TJ /F5 1 Tf 37.6033 0 TD (p)Tj /F10 1 Tf .6565 0 TD (<)Tj /F4 1 Tf .7083 0 TD [(0.)24.4(05)26.8(\).)-384.4(A)15.5(L)0(P)20.1(,)-389.2(al)19.7(k)16.3(a)0(l)19.7(i)0(n)26.6(e)-393.7(ph)26.8(os)21.2(-)]TJ -38.9681 -1.0077 TD [(ph)21.1(a)15.1(t)0(a)19.7(s)0(e)25.8(;)-323.6(BD)25(NF)20.4(,)-320.1(b)0(r)21.1(a)15.1(in)20.9(-d)26.8(er)19.9(iv)26.6(ed)-314.1(n)16.3(e)0(u)19.9(r)0(o)26.8(t)0(r)20.9(o)0(p)26.8(h)0(i)20.9(c)-324.6(f)16.3(a)0(c)18.7(t)16.1(or)21.1(;)-323.7(C)15.3(M,)-310.4(cu)19.9(l)16.1(t)0(u)20.9(r)0(e)-308.4(m)0(e)18.7(d)16.3(iu)20.9(m)15.1(;)-323.7(hB)25.8(MS)20.4(Cs)26(,)-325.9(h)16.3(um)19.9(a)15.1(n)-323.5(bo)21.1(n)16.3(e)-324.6(m)15.1(e)0(s)20.1(e)0(n)25.6(c)0(h)19.9(y)0(m)25.6(a)0(l)-314.3(s)16.4(te)19.7(m)-318.9(c)0(e)18.7(l)16.1(ls)21(.)]TJ ET q 1 i 62.589 281.707 m 300.529 281.707 l 300.529 162.992 l 62.589 162.992 l W n q 238.023 0 0 118.715 62.589 162.992 cm /Im2 Do Q Q BT /F7 1 Tf 9.845 0 0 9.845 62.022 146.211 Tm [(FIG.)-607.4(2.)]TJ /F5 1 Tf 4.3823 0 TD (ALP)Tj /F4 1 Tf 2.3898 0 TD [(gene)-605.2(expression)-605.2(and)-603(mineralized)-610.4(nodule)]TJ -6.772 -1.0077 TD [(formation)-334.1(after)-335.7(stimulation)-330.6(by)-336(BDNF.)]TJ /F7 1 Tf 15.8878 0 TD (\(A\))Tj /F4 1 Tf 1.716 0 TD [(Three)-336.7(days)-327.4(after)]TJ -17.6039 -1.0135 TD [(100)-170(ng/mL)-272.3(BDNF)-277.1(treatment,)-276.6(RT-PCR)-274.8(revealed)-283.4(signicantly)]TJ T* (more)Tj /F5 1 Tf 2.3783 0 TD (ALP)Tj /F4 1 Tf 2.0961 0 TD [(mRNA)-318.7(expression)-317.3(compared)-323.6(to)-313.1(the)-315.3(other)-323(groups)]TJ -4.4744 -1.0135 TD (\(*)Tj /F5 1 Tf .835 0 TD (p)Tj /F10 1 Tf .668 0 TD (<)Tj /F4 1 Tf .7141 0 TD (0.05\).)Tj /F7 1 Tf 2.9138 0 TD (\(B\))Tj /F4 1 Tf 1.9118 0 TD [(Matrix)-578.4(mineralization)-579.2(nodule)-583.1(assays)-577.9(re-)]TJ -7.0427 -1.0077 TD [(vealed)-297.6(more)-300(nodule)-295.2(formation)-299.5(in)-295.8(the)-298(groups)-293.7(treated)-298.7(with)-298.8(50)]TJ 0 -1.0135 TD [(and)-251.8(100)-164.2(ng/mL)-249.3(BDNF)-254(relative)-248.1(to)-249.8(the)-251.9(OM)-245.5(and)-251.8(CM)-251.4(groups)-247.6(by)]TJ T* [(day)-395.7(14.)-396.9(OM,)-392.8(osteogenic)-399.4(differentiation)-399.3(medium;)-396.6(RT-PCR,)]TJ 0 -1.0077 TD [(real-time)-273.3(polymerase)-268(chain)-266.6(reaction.)-274.3(Color)-265.3(images)-268.6(available)]TJ 0 -1.0135 TD [(online)-335.7(at)-331.6(www.liebertpub.com/tea)]TJ /F8 1 Tf 8.9663 0 0 8.9663 62.022 749.6502 Tm (1286)Tj 49.4894 0 TD [(LIU)-334.5(ET)-338.7(AL.)]TJ ET endstream endobj 54 0 obj <>stream AdobedC        s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?^sN5~q[lUg1|~fiz?uKۻ5i2Tǟf͛6lٲ ~x~SZ֙FĜD4e4B68c?+4a8?-<ɫEhz:Emד}eɆM_I`}B1K5 ʾ&0y`ٱ BBn#4$k^݀+K8xRK+* ,B7&43PƥUUQRXZ լ'8ݏq]C[tD/PLkq2DXCZb:Fd54gEA% [Y\4V-w)oJp i~[h漢VA8_2+sOZj ]20X2MpO?+,Vm"E^HH_߯?8zSޝySޙwb6+iX;tEEX`ٳf͛6lAqqm/2\JCI ђU*yk?T__KJIigSF<2_ O>~nk|ѧX,,b MF,H)cF\ٳf,qFh ;T $麌Xἷ_ZE9+WҮ/f omIQƀ_`ٳf͛6lٳf͛6lٳf͛6lٳf͛6lo纻l+o-f5I?|~lyS򖷦yKPľR+[k6KvG^^T({>jGVg6vQ[XZii*!'?<<Z=x.;v]\QYx(\;cFoyGƗws0 "ruv;u\ u cQ{7zWRl,.cZ/h?:' E6Sw4mpK$Yx#S{[tO&Ki Up"JѶȮ5:4+-?KW\wMqk,Qz+IAMMKyDݍגoǨM .c@15 p6yNe$}Iթ$[zvǭ=iڇ,OΟ(.k^S}#og p]\FZk+J];y>l+]cL:=SiI-:j? ᑖ;怯巚}Pb$˒Ŭ-b֖K5rY>&n[mk~Zie\MP7fU4Ev ħG4/˟=3PM"gSM 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7RANr;xiFS?բ[{Qp*V5E4#b͊6*ثb͊6*ثb͊6*ثb͊6*ثb͊6*ثb͊6*ثb&aF2Gbǜ4)(kZ}\PUPpaQ@$``R͊6*ثb͊6*EAM-.[Ȩ59d A*AVGB3u[ʨ]d鿷ceÿG&r~J* z#.h}9D&$9 1 y dhN5ǎ5FU#D{ɐD@<\I*G* e%rN%bǗTw><vjLlєMAjTk[շPlշ=N'|hH˛hp]Wm Xꅗ}`+/,8sDwzUecNRL숽ُALyfΚƦeimn:D2clg?Ԑy^:N!X5 !{}>stream /GS1 gs BT /F4 1 Tf 9.843 0 0 9.843 59.7543 419.4141 Tm 0 0 0 rg 0 Tc 0 Tw [(neurogenic)-636.7(neuron-rela)-9.9(ted)-632.4(proteins)-632.1(compared)-641.3(with)-633.3(cells)]TJ 0 -1.1116 TD [(grown)-317.4(in)-313.3(CM)-309.4(or)-313.2(OM)-315(only,)-313.2(or)-313.2(50)-163.5(ng/mL)-319.1(BDNF)-312.3(\(Fig.)-313(4\).)-310.9(By)]TJ T* [(day)-252.1(7,)-246.4(protein)-251(expression)-255(of)-249.8(the)-246.5(neuron)-255.4(cell)-248.9(markers)-252.9(p75)-245.2(and)]TJ 0 -1.1174 TD [(s100)-321(was)-316.2(much)-317.8(higher)-318.9(in)-319.1(the)-315.6(group)-322.3(treated)-316.7(with)-322.3(100)-164.6(ng/mL)]TJ 0 -1.1116 TD [(BDNF)-392.9(relative)-392.8(to)-388.2(50)-169.2(ng/mL)-388.2(BDNF)-392.9(or)-388.1(cells)-388(in)-388.2(OM)-389.9(or)-388.1(CM)]TJ T* [(without)-377.6(BDNF.)-373.3(However,)-378(protein)-377.7(expression)-375.9(did)-372.1(not)-372.1(show)]TJ 0 -1.1174 TD [(an)-337.4(increasing)-337.1(trend)-335.1(on)-330.5(day)-338.5(14)-330.5(\(Fig.)-336.1(4\).)]TJ /F11 1 Tf 8.9663 0 0 8.9663 310.8472 420.0377 Tm [(Effect)-334.9(of)-330.4(BDNF)-338(on)-331.3(the)-334.8(ectopic)-335.3(bone)-333.8(formation)]TJ 0 -1.2203 TD [(capacity)-334.8(of)-330.4(hBMSCs)]TJ /F4 1 Tf 9.843 0 0 9.843 320.8251 387.1558 Tm -.0165 Tc [(A)-16.5(s)-382.2(sho)5.4(w)-1.2(n)-368.9(i)5.3(n)-368.9(F)-.2(ig)5.4(ure)-364.3(5,)-365.5(H&E)-364.4(s)-.1(taini)5.3(n)-.3(g)-368.9(r)5.5(evealed)-368.9(n)-.3(o)-363.2(obv)5.4(iou)5.4(s)]TJ -1.0137 -1.1116 TD -.0156 Tc [(i)6.2(n).6(a)5.2(mm)5.1(ati)6.2(o).6(n)-506.3(a)-.6(t)-506.4(4)-506.3(and)-506.3(8)-506.3(w)-.3(ee)5.2(ks.)-502.8(F).7(ou)6.3(r)-512(w)5.5(eek)6.3(s)-511.8(a)5.2(fte)5.2(r)]TJ /F5 1 Tf 21.4146 0 TD -.0203 Tc [(in)-516.7(vivo)]TJ /F4 1 Tf -21.4146 -1.1116 TD -.0158 Tc [(t)6(r).4(an)6.1(spla)5(nt)6(ati)6(on,)-347.5(muc)5(h)-351(les)6.3(s)-356.5(n)6.1(e)-.8(wl)6(y)-351(for)6.2(med)-351(t)6(i).3(ssu)6.1(e)-352.1(w)-.5(as)-350.8(o)6.1(b).4(se)5(rve)5(d)]TJ T* -.0162 Tc [(i)5.6(n)-299.5(g)5.7(rou)5.7(ps)-299.3(I)-293.7(\()]TJ /F6 1 Tf 4.8785 0 TD 0 Tc (b)Tj /F4 1 Tf .5299 0 TD -.017 Tc [(-TCP)-300.2(o)4.9(n)-.8(ly)4.9(\))-300.3(a)3.8(nd)-294.6(II)-294.5(\()]TJ /F6 1 Tf 7.6489 0 TD 0 Tc (b)Tj /F4 1 Tf .5357 0 TD -.022 Tc [(-T)-7(C)-6.8(P)]TJ /F10 1 Tf 2.0908 0 TD 0 Tc (+)Tj /F4 1 Tf .5357 0 TD -.0162 Tc [(CM)-294.7(on)5.7(ly\))-293.7(r)0(elat)5.6(ive)-294.9(t)5.6(o)]TJ ET q 360.926 0 0 281.083 59.754 450.935 cm /Im3 Do Q BT /F7 1 Tf 9.845 0 0 9.845 433.1337 663.0801 Tm 0 Tc [(FIG.)-336.7(3.)]TJ /F4 1 Tf 4.1174 0 TD (Erk/Runx2/Osterix)Tj -4.1174 -1.0135 TD [(expression)-334.5(after)]TJ /F5 1 Tf 6.7893 0 TD (TrkB)Tj /F4 1 Tf -6.7893 -1.0135 TD [(knockdown.)-336.7(Forty-eight)]TJ T* [(hours)-333(after)-335.7(transfection)-338.2(of)]TJ 0 -1.0077 TD [(100)-170(nM)-331(siRNA-TrkB,)-334.8(RT-)]TJ 0 -1.0135 TD [(PCR)-333(revealed)-341(signicantly)]TJ T* (less)Tj /F5 1 Tf 1.8312 0 TD (TrkB)Tj /F4 1 Tf 2.338 0 TD [(mRNA)-336(expression)]TJ /F7 1 Tf -4.1692 -1.0077 TD (\(A\))Tj /F4 1 Tf 1.3878 0 TD (,)Tj /F5 1 Tf .5816 0 TD (Runx2)Tj /F4 1 Tf 2.8965 0 TD (expression)Tj /F7 1 Tf 4.6126 0 TD (\(B\))Tj /F4 1 Tf 1.336 0 TD (,)Tj -10.8145 -1.0135 TD (and)Tj /F5 1 Tf 1.7794 0 TD (Osterix)Tj /F4 1 Tf 3.2824 0 TD (expression)Tj /F7 1 Tf 4.6126 0 TD (\(C\))Tj /F4 1 Tf -9.6744 -1.0135 TD [(compared)-335.1(to)-336.2(NC)-332(group)]TJ T* (\(*)Tj /F5 1 Tf .835 0 TD (p)Tj /F10 1 Tf .668 0 TD (<)Tj /F4 1 Tf .7141 0 TD (0.05\).)Tj /F7 1 Tf 2.6662 0 TD (\(D\))Tj /F4 1 Tf 1.7218 0 TD (Western)Tj -6.6051 -1.0077 TD [(blotting)-336.9(assays)-336(showed)-336(less)]TJ 0 -1.0135 TD [(expression)-334.5(of)-336(TrkB)-334.4(protein,)]TJ T* [(p-Erk1/2,)-248.7(Runx2,)-245.4(and)-246(Osterix)]TJ T* [(in)-336.2(the)-332.6(48-h)-332.2(siRNA-TrkB)]TJ 0 -1.0077 TD (group.)Tj ET q 336.928 0 0 272.296 59.754 56.636 cm /Im4 Do Q BT /F7 1 Tf 9.845 0 0 9.845 409.0959 249.6188 Tm [(FIG.)-336.7(4.)]TJ /F4 1 Tf 4.1174 0 TD [(Neuronal)-333.7(marker)-337.7(expres-)]TJ -4.1174 -1.0077 TD [(sion)-332.2(in)-336.2(hBMSCs)-336.6(stimulated)-336.4(by)]TJ 0 -1.0135 TD [(BDNF.)-326.5(p75)-325.4(\()]TJ /F5 1 Tf 5.39 0 TD (green)Tj /F4 1 Tf 2.2804 0 TD [(\))-323.5(and)-320.9(s100)-326.3(\()]TJ /F5 1 Tf 4.9696 0 TD (red)Tj /F4 1 Tf 1.3302 0 TD (\))Tj -13.9702 -1.0135 TD [(expression)-334.5(in)-336.2(hBMSCs)-336.6(at)-331.6(7)-335(and)]TJ T* [(14)-238.1(days)-246.8(after)-237.8(stimulation)-244.3(by)-243.8(BDNF.)]TJ 0 -1.0077 TD [(Immunouorescent)-338.2(staining)-337.7(re-)]TJ 0 -1.0135 TD [(vealed)-337.9(that)-333.7(100)-164.2(ng/mL)-335.7(BDNF)-334.7(led)]TJ T* [(to)-336.2(more)-334.5(p75)-331.2(and)-332.4(s100)-337.8(protein)-330.9(ex-)]TJ 0 -1.0077 TD [(pression)-337.2(relative)-334.4(to)-336.2(CM,)-335.4(OM,)-329.5(and)]TJ 0 -1.0135 TD [(50)-169(ng/mL)-329.9(BDNF)-340.4(\(scale)-331.9(bar)-338.1(repre-)]TJ T* [(sents)-334.2(40)]TJ /F6 1 Tf 3.5012 0 TD (m)Tj /F4 1 Tf .5528 0 TD [(m\).)-334.8(Color)-334.4(images)-331.9(avail-)]TJ -4.054 -1.0135 TD [(able)-334.7(online)-335.7(at)-337.3(www.liebertpub)]TJ 0 -1.0077 TD (.com/tea)Tj /F8 1 Tf 8.9663 0 0 8.9663 59.7543 749.7069 Tm [(EFFECT)-338(OF)-337.5(BDNF)-330.2(ON)-334.6(BONE)-335.4(NEUROGENESIS/OSTEOGENESIS)-22070.5(1287)]TJ ET endstream endobj 61 0 obj <>stream AdobedC       J s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?|k*`ZpT"vy{3*#F-΋XMn 2˞OnߚbOoo&OUq*ɨ+Ȯ/FPe&d%[cB:ǐ|9_/.jaidz[F/oGpY}h_cyVBlyf͛6lٳf͛6lٳ`=kR]/G3*rba ]^9έ6ܷ P29 _'KEu J"ȥP4玹֞e: H*<|~]Zq4Zv{(j[Yk 8vhՊ9\ 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[(mL)-425.1(BDNF)-421.7(group)-420.2(and)-419.2(group)-420.2(III.)-421.3(There)-423.7(were)-422.3(no)-422.7(statistical)]TJ T* [(differences)-339.2(betwe)-8.8(en)-331.7(4)-335.2(and)-332.8(8)-329.4(weeks)-336.8(across)-336.8(all)-338.8(groups.)]TJ 1.0137 -1.1174 TD [(Fi)20.9(na)25.4(ll)20.6(y)16.2(,)-429.6(im)19.5(m)15(u)0(n)20.8(o)16.2(hi)20.7(st)26.7(oc)19.7(he)25.4(mi)19.5(c)15(a)0(l)-418.2(s)0(t)20.9(a)0(i)25.3(n)0(i)20.7(n)0(g)-416.9(a)15(nd)-416.9(se)19.9(m)15(i)0(q)20.7(u)0(a)25.4(n)0(t)20.7(i)0(t)26.3(a)0(-)]TJ -1.0137 -1.1116 TD [(ti)20.6(ve)-360.5(an)25.4(al)19.6(ys)26.8(is)-359.2(of)-359.3(se)19.9(ve)25.4(ra)19.7(l)-369.9(o)0(t)20.7(h)16.2(er)-360.4(ne)19.7(u)16.2(r)0(o)20.9(n)-369.7(ma)24.2(rk)20.9(er)19.7(s)-369.5(\()0(G)25.8(F)0(A)20.1(P)0(,)-355.7(N)0(G)19.1(2)0(,)]TJ T* [(an)19.7(d)]TJ /F6 1 Tf 1.7797 0 TD (b)Tj /F4 1 Tf .5414 0 TD [(-t)26.5(ub)20.8(ul)26.5(in)-342.1(II)20.9(I\))-342(sh)21(o)16.2(w)0(e)18.8(d)-352.4(th)20.7(a)15(t)-358.3(b)16.2(o)0(t)20.7(h)-352.4(GF)20.1(A)15.3(P)-358(a)15(n)0(d)]TJ /F6 1 Tf 17.0084 0 TD (b)Tj /F4 1 Tf .5414 0 TD -.0177 Tc [(-)-17.7(t)3(ub)-17.7(ul)-17.7(i)8.6(n)-375.9(II)-17.7(I)]TJ -19.871 -1.1116 TD 0 Tc [(\(T)19.7(UB)24.7(B\))-440.9(ex)25.4(pr)20.9(es)19.9(s)16.4(i)0(o)20.7(n)0(s)-439.7(w)15.3(er)19.7(e)-451.5(h)0(i)26.5(g)0(h)20.8(e)0(r)-441.1(i)16.1(n)-450.4(g)0(r)20.9(o)0(u)26.6(p)-450.3(IV)-440.8(at)-441.2(4)-450.4(w)0(e)24.6(e)0(k)19.7(s)0(,)]TJ ET q 1 i 96.775 732.245 m 517.436 732.245 l 517.436 371.225 l 96.775 371.225 l W n q 420.92 0 0 361.02 96.775 371.225 cm /Im5 Do Q Q BT /F7 1 Tf 9.845 0 0 9.845 62.022 354.444 Tm [(FIG.)-319.5(5.)]TJ /F4 1 Tf 4.1001 0 TD 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yp533}n!Vx4Qemu_J:A#'u1_mXmRLVI_7o.,)?+Aߤ/kF7- h#1P@1Jf*(رڸ*vlUٱWf]vlUٱWf]vlUٱWf]vlUٱWf]vlUٱWd|SC?=>{khh;Ɂf]vlUٱWf]_?ӿG Ig?k& >{CHe<_ox,<tx Wo ;ޢ)Zӽ+TNxl [Cm4s&6 JaGA3K1fnjd SB DlDv=9ou.9OH]-*O oz"in^I./o^ynO# ^̺ؒ욈M>cNEmm- SIlUٱWf]vlUٱWf]vlUٱWf]vlUٱWf]vlUٱWf]/.ڎduxĄeW5*_ #$,S%=kױI=HEQ<_C1ܢ${ `Pɩ'Z͊6*ثb͊"Pԧ~kd(KssfS<}txU'K{{2R4 OgoH| %?R{'{ Zo0fun9lpKrD?ʴkW ڥF" S| 9z=n"6Q/znğ$cYWf]vlU󗖯/k$h4RPZ8 @~/B7>stream /GS1 gs BT /F4 1 Tf 9.843 0 0 9.843 62.022 122.3433 Tm 0 0 0 rg 0 Tc 0 Tw [(siRNA-TrkB)-545.8(to)-538(knockdown)-541.9(the)-540.2(BDNF)-536.9(receptor)-542.3(gene)-542.4(in)]TJ 0 -1.1116 TD .0204 Tc [(BD)-4.6(NF-trea)-4.9(t)1.9(ed)-326.3(B)-4.8(M)1.1(SCs,)-322.9(a)-4.9(n)2(d)-326.3(d)2(e)-4.9(t)1.9(ected)-326.3(the)-327.4(e).9(xpression)-326.3(l)1.9(evel)]TJ 0 -1.1174 TD .0187 Tc [(of)-518(p)-5.4(-).4(Er)-5.4(k1/2)-5.4(,)-514.6(Er)-5.4(k1/)-5.6(2,)-520.4(and)-518(t).2(h)-5.4(e)-519.2(down)-5.4(s).5(tr)-5.4(eam)-519.3(tr)-5.4(ans)-5.2(c)-.8(ri)-5.6(ptio)-5.4(n)]TJ 0 -1.1116 TD [(fa)-6.7(cto)-5.5(r).3(s)-350.9(R)-.8(un)-5.5(x2)-351.1(and)-351.1(O)-6.4(ste)-6.7(r).3(ix)-5.5(.)-347.7(I).3(n)-351.1(a)-6.7(ddit)-5.7(i).1(on)-5.5(,)-347.7(W)-2(es)-5.3(ter)-5.5(n)-351.1(blo)-5.5(ttin)-5.5(g)]TJ T* .0202 Tc [(re)-5.1(sults)-366.6(r)1.9(eveale)-5.1(d)-361(that)-366.9(after)-366.8(knocking)-366.8(down)-366.8(t)1.7(he)]TJ /F5 1 Tf 19.8883 0 TD .0218 Tc [(Tr)3.6(kB)]TJ /F4 1 Tf 2.4479 0 TD .0184 Tc [(ge)-6.9(ne)]TJ -22.3361 -1.1174 TD .0187 Tc [(wi)-5.6(th)-339.5(t)-5.6(h).3(e)-346.4(s).5(iRN)-6.3(A)-.5(,)-341.8(p).3(h)-5.4(o).3(sp)-5.4(ho-)-5.4(Erk1)-5.4(/2)-345.3(expr)-5.4(ess)-5.2(i).2(on)-345.3(was)-345.1(n).3(o)-5.4(t).2(abl)-5.6(y)]TJ 0 -1.1116 TD .0201 Tc [(de)-5.2(crea)-5.2(sed,)-432.6(a)-5.2(n)1.7(d)-436(R).7(T-PCR)-437(a)-5.2(nd)-436(Western)-436(b)1.7(lotting)-436(a).6(ssay)-436(re)-5.2(-)]TJ 25.504 6.6813 TD .0187 Tc [(s)-5.2(u).3(lt)-5.6(s)-402.7(r).4(e)-6.6(v).3(eal)-5.6(ed)-402.9(tha)-6.6(t)-403(the)-404(e)-6.6(xpr)-5.4(ess)-5.2(i).2(on)-402.9(of)-408.6(Runx)-5.4(2)-402.9(a)-.8(nd)-402.9(O)-6.3(s).5(ter)-5.4(i).2(x)]TJ 0 -1.1116 TD [(w)-6.2(a)-.7(s)-350.7(m)-.8(ark)-5.3(e)-.7(dl)-5.5(y)-345.2(r)-5.3(educ)-6.5(ed)-350.9(at)-351.1(both)-5.3(,)-347.5(th)-5.3(e)-346.3(g).4(e)-6.5(n).4(e)-352.1(a)-.7(nd)-350.9(pro)-5.3(t).3(ei)-5.5(n)-345.2(l)-5.5(ev-)]TJ 0 -1.1174 TD [(e)-6.7(l).1(s.)-485.9(H)-6.4(e)-.9(nce)-6.7(,)-485.9(our)-489.3(stu)-5.5(d).2(y)-483.6(e)-6.7(luci)-5.7(dat)-5.7(e)-.9(s)-483.4(a)-490.5(pos)-5.3(sib)-5.5(l).1(e)-484.8(m)-1(e)-6.7(c)-.9(han)-5.5(i).1(sm)]TJ 0 -1.1116 TD .023 Tc [(un)4.6(d)4.6(e)-2.3(r)4.7(l)4.5(yi)4.5(n)4.6(g)-433.1(t)4.5(h)4.6(e)-434.3(o)4.6(st)4.5(eog)4.6(e)3.5(nes)4.8(i)4.5(s-)4.7(pr)4.7(o)4.6(m)3.4(ot)4.5(i)4.5(n)-1.1(g)-427.4(e)3.5(ff)4.7(ect)-427.5(o)-1.1(f)-427.3(B)-2.2(DNF.)]TJ T* .0189 Tc [(H)-6.1(o).5(we)-6.4(ver,)-370.4(a)-375(c)-.6(omp)-5.2(l).4(et)-5.4(e)-369.3(e)-.6(xp)-5.2(eri)-5.4(m)-.7(ent)-5.4(,)-364.7(i)-5.4(nvo)-5.2(lvi)-5.4(n).5(g)-368.1(t)-5.4(he)-369.3(ap)-5.2(pli)-5.4(ca-)]TJ 0 -1.1174 TD .0184 Tc [(t)-5.9(i)-.1(on)-293.7(of)-293.7(pa)-6.9(thw)-6.6(a)-1.1(y)-288(i)-5.9(nhi)-5.9(bit)-5.9(o)0(rs)-5.5(,)-290.3(i)-.1(s)-293.5(r).1(e)-6.9(qui)-5.9(red)-293.7(t)-.1(o)-293.7(f).1(ur)-5.7(the)-6.9(r)-287.9(i)-5.9(llu)-5.7(str)-5.7(a)-1.1(te)]TJ 0 -1.1116 TD .023 Tc [(th)4.6(e)-330.6(p)4.6(at)4.5(h)4.6(w)-2(ay)4.6(.)]TJ ET q 420.92 0 0 527.244 96.775 205.002 cm /Im7 Do Q BT /F7 1 Tf 9.845 0 0 9.845 62.022 188.2204 Tm 0 Tc [(FIG.)-342.5(7.)]TJ /F4 1 Tf 4.1231 0 TD [(Immunohistochemical)-350(staining)-343.4(of)-341.7(GFAP,)-342.6(NG2,)-342(and)]TJ /F6 1 Tf 21.4679 0 TD (b)Tj /F4 1 Tf .5528 0 TD [(-tubulin)-342.4(III.)]TJ /F7 1 Tf 5.1078 0 TD (\(A\))Tj /F4 1 Tf 1.7276 0 TD [(Immunohistochemical)-350(staining)-343.4(of)-341.7(GFAP,)]TJ -32.9792 -1.0135 TD [(NG2,)-238.3(and)]TJ /F6 1 Tf 4.1116 0 TD (b)Tj /F4 1 Tf .5528 0 TD [(-tubulin)-233(III)-239.1(\(TUBB\))-240.3(at)-239.4(4)-237.1(and)-240.2(8)-237.1(weeks)-238.3(\(scale)-239.8(bar)-240.2(represents)-237.8(50)]TJ /F6 1 Tf 24.6466 0 TD (m)Tj /F4 1 Tf .5528 0 TD [(m\).)-236.9(The)-235.7(average)-242(optical)-240.1(density)-238.6(of)]TJ /F7 1 Tf 13.9414 0 TD (\(B\))Tj /F4 1 Tf 1.5721 0 TD (GFAP,)Tj /F7 1 Tf 3.029 0 TD (\(C\))Tj /F4 1 Tf -48.4063 -1.0077 TD [(NG2,)-267.1(and)]TJ /F7 1 Tf 4.1634 0 TD (\(D\))Tj /F6 1 Tf 1.6469 0 TD (b)Tj /F4 1 Tf .5528 0 TD [(-tubulin)-261.8(III)-262.1(\(TUBB\))-269.1(immunohistochemical)-269.5(staining)-262.8(\(*)]TJ /F5 1 Tf 21.7615 0 TD (p)Tj /F10 1 Tf .668 0 TD (<)Tj /F4 1 Tf .7141 0 TD [(0.05)-265.5(compared)-266(to)-261.3(Group)-264.9(I,)]TJ 7.3837 0 0 6.5625 460.2329 172.6866 Tm (^&)Tj /F5 1 Tf 9.845 0 0 9.845 469.4739 168.3212 Tm (p)Tj /F10 1 Tf .668 0 TD (<)Tj /F4 1 Tf .7198 0 TD [(0.05)-259.7(compared)-266(to)]TJ -42.7745 -1.0135 TD 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-1.1116 TD [(higher)-244(in)-244.2(BDNF-treated)-249.9(cells)-244(at)-245.4(4)-243(and)-240.6(8)-243(weeks.)-248.1(We)-241.8(therefore)]TJ T* [(conclude)-265.9(from)-264.7(these)]TJ /F5 1 Tf 8.4264 0 TD [(in)-261.5(vivo)]TJ /F4 1 Tf 2.9835 0 TD [(studies)-267.9(and)-263.6(histological)-263.7(staining)]TJ -11.41 -1.1174 TD [(that)-495.4(both)-494.1(osteogenesis)-500.2(and)-494(neurogenesis)-500.2(tend)-495.3(to)-491.9(increase)]TJ 0 -1.1116 TD [(after)-336.2(BDNF)-335.3(treatment.)]TJ 1.0137 -1.1116 TD [(However,)-395.3(in)-394(the)]TJ /F5 1 Tf 7.1017 0 TD [(in)-394(vitro)]TJ /F4 1 Tf 3.4616 0 TD (and)Tj /F5 1 Tf 1.8373 0 TD [(in)-394(vivo)]TJ /F4 1 Tf 3.2427 0 TD [(results)-394.6(obtained)-391.5(in)]TJ -16.6571 -1.1174 TD [(this)-378.8(study,)-383.3(we)-378.6(are)-380(not)-377.8(able)-381.2(to)-376.7(explain)-378.9(whether)-385.4(BDNF)-375.6(pro-)]TJ 0 -1.1116 TD [(moted)-359.4(BMSC)-352.8(neurogenesis)-362(by)-353.5(directly)-357.1(inducing)-355.8(differenti-)]TJ T* [(ation)-248.8(into)-246.6(neurons)-244.8(or)-244.1(by)-244.1(indirectly)-250(helping)-245.3(BMSCs)-250(to)-227(se)19.9(cr)19.7(et)19.5(e)]TJ 0 -1.1174 TD [(ne)19.7(ur)15.1(op)20.8(ro)20.9(te)19.6(ct)19.5(iv)20.7(e)-560.9(f)0(a)19.7(c)0(t)19.5(o)0(r)15.1(s)-559.6(th)20.7(at)-550.7(co)19.7(ul)20.7(d)-559.8(i)0(n)20.7(d)0(u)20.8(c)0(e)-551.7(n)0(e)19.7(a)0(r)19.7(b)0(y)-549.4(c)0(e)18.5(l)0(l)20.6(s)-559.6(to)]TJ 0 -1.1116 TD [(di)14.9(ff)20.9(er)19.7(en)19.7(ti)20.6(at)19.5(e)-445.8(i)0(n)20.7(t)0(o)-434.3(n)0(e)19.7(r)0(v)20.9(e)-445.8(ce)18.5(ll)20.6(s.)-430.6(Re)18.6(fe)19.7(rr)15.2(in)20.7(g)-438.8(t)0(o)-434.3(p)0(r)20.9(e)0(v)13.9(i)0(o)20.7(u)0(s)-428.2(s)0(t)15.1(u)0(d)20.8(i)0(e)19.5(s)]TJ T* [(th)15(at)-441.2(ha)19.7(ve)-441.1(re)19.7(po)20.8(rt)20.7(ed)-446.9(ab)19.7(ou)20.8(t)-450.5(t)0(h)20.7(e)-451.5(po)20.8(ss)15.5(ib)20.7(il)20.6(it)20.6(y)-450.4(o)0(f)-439.9(b)0(o)20.8(t)0(h)-445.8(t)0(h)20.7(e)-451.5(ab)19.7(ov)20.8(e)]TJ 0 -1.1174 TD [(wa)18.8(ys)15.3(,)]TJ 7.3823 0 0 6.5614 81.9212 466.5258 Tm [(36)24.7(3)24.7(9)]TJ 9.843 0 0 9.843 104.9385 462.1038 Tm [(we)-493.8(sp)21(ec)18.5(ul)15(at)19.5(e)-497.6(t)0(h)20.7(a)0(t)-493.1(t)0(h)20.7(e)0(s)19.9(e)-503.4(tw)19.8(o)-502.2(w)0(a)18.8(y)0(s)-491.6(a)0(c)18.5(t)-502.3(si)20.9(mu)19.6(lt)20.6(a-)]TJ -4.5905 -1.1116 TD [(ne)19.7(ou)15.1(sl)20.9(y)-352.4(a)0(n)19.7(d)-346.7(in)-342.1(a)-353.6(s)0(y)21(n)0(e)19.7(r)0(g)20.9(i)0(s)20.9(t)0(i)14.8(c)-347.8(or)-342(co)19.7(mp)19.6(li)20.6(ca)18.5(te)19.6(d)-352.4(m)0(a)18.4(n)0(n)20.8(e)0(r)19.7(.)-349(T)15(h)21.9(i)21.8(s)-340.7(i)21.8(s)]TJ T* -.0206 Tc [(because)-483.6(apart)-476.8(from)-477.9(our)]TJ /F5 1 Tf 9.9931 0 TD -.0219 Tc [(in)-478(v)-6.9(itro)]TJ /F4 1 Tf 3.4904 0 TD -.0186 Tc [(I)3.4(F)-474.5(ass)3.5(a)2.2(y)3.3(,)-477(in)-474.7(wh)3.3(ich)-474.7(n)3.3(eur)3.4(o)3.3(n)]TJ -13.4835 -1.1116 TD -.0209 Tc 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[(an)19.7(d)-254.5(o)0(u)20.8(r)-254.5(H&)18.7(E)-255.7(s)0(t)20.9(a)0(i)19.5(n)0(i)20.7(n)0(g)-249.9(r)0(e)19.7(v)0(e)19.7(a)0(l)19.6(e)0(d)-245.3(t)0(h)20.7(a)0(t)]TJ -10.2638 -1.1116 TD [(BD)18.9(NF)-452.2(sh)21(ow)20(ed)-452.6(th)20.7(e)-457.3(t)0(e)19.6(n)0(d)20.8(e)0(n)19.7(c)0(y)-452.6(t)0(o)-445.8(p)0(r)20.9(o)0(m)19.6(o)0(t)20.7(e)-463(th)20.7(e)-457.3(g)0(e)19.7(n)0(e)19.7(r)0(a)19.7(t)0(i)14.8(o)0(n)-445.7(o)0(f)]TJ T* [(mo)19.6(re)-274(ca)18.5(pi)20.7(ll)20.6(ar)14(ie)19.5(s)-277.4(w)0(i)19.8(t)0(h)15(i)0(n)-267.3(n)0(e)19.7(w)-284.2(bo)20.8(ne)-274.1(ti)20.6(ss)21.2(ue)-274.1(by)-267.1(8)-283.3(w)0(e)18.8(e)0(k)19.7(s)-283.1(al)19.6(th)20.7(ou)20.8(gh)]TJ 0 -1.1174 TD [(th)15(er)19.7(e)-330.6(w)0(e)18.8(r)0(e)-320.1(n)0(o)-319(s)0(i)20.9(g)0(n)15.1(i)0()20.9(c)0(a)18.5(n)0(t)-319.1(d)0(i)20.7(f)0(f)20.9(e)0(r)14(e)0(n)19.7(c)0(e)18.5(s)-329.2(\(d)20.9(at)19.5(a)-330.6(n)0(o)20.8(t)-335.3(sh)21(ow)20(n\))20.9(.)-331.7(C)0(o)19.8(n)0(-)]TJ 0 -1.1116 TD [(si)15.1(de)19.7(ri)20.7(ng)-388.1(an)19.7(im)19.5(al)-389.4(et)19.5(hi)15(cs)-389.1(an)19.7(d)-398.5(w)0(e)18.8(l)0(f)20.7(a)0(r)19.7(e)0(,)-391.6(w)0(e)-390.1(u)0(s)21(e)0(d)-389.3(s)0(i)15.1(x)-398.5(an)19.7(im)19.5(al)19.5(s)-398.3(i)0(n)]TJ T* [(on)15.1(e)-411.2(g)0(r)20.9(o)0(u)20.8(p)0(,)-401.9(a)0(n)19.7(d)-410(th)20.7(er)14(ef)19.7(or)20.9(e,)-403.1(th)20.7(e)-411.2(r)0(e)19.7(a)0(s)14.1(o)0(n)-399.6(f)0(o)20.9(r)-410(no)-405.4(si)20.9(gn)20.8(i)20.9(ca)18.5(nt)-405.5(di)20.7(f-)]TJ 0 -1.1174 TD [(fe)14(re)19.7(nc)19.7(es)-285.4(ma)18.4(y)-289.1(l)0(i)20.6(e)-296(in)-284.6(th)20.7(e)-296(s)0(m)19.8(a)0(l)19.5(l)-295(nu)20.8(mb)19.6(er)-285.6(of)-278.6(sa)14.1(mp)19.6(le)19.6(s.)-280.8(In)-284.4(th)20.7(e)-296(n)0(e)19.7(x)0(t)]TJ 0 -1.1116 TD [(st)15.1(ep)19.7(,)-343.2(w)0(e)-338.3(w)0(i)19.8(l)0(l)-336.5(i)0(n)20.7(v)0(e)19.7(s)0(t)15.1(i)0(g)20.7(a)0(t)19.5(e)-347.8(th)20.7(e)-347.8(r)0(e)19.7(l)0(a)19.6(t)0(i)20.6(o)0(n)20.8(s)0(h)21(i)0(p)-336.4(b)0(e)19.7(t)0(w)14.1(e)0(e)18.5(n)-340.9(ne)13.9(ur)20.9(og)20.8(en)19.7(-)]TJ T* [(es)14.1(is)-313.2(an)19.7(d)-323.6(a)0(n)19.7(g)0(i)20.7(o)0(g)20.8(e)0(n)19.7(e)0(s)19.9(i)0(s)-313.2(b)0(y)-313.2(u)0(s)15.3(i)0(n)20.7(g)-323.6(BD)18.9(NF)-313.9(in)-313.3(bo)20.8(ne)-314.4(en)19.7(gi)20.7(ne)19.7(er)19.7(in)20.7(g.)]TJ 1.0137 -1.1174 TD [(In)-347.7(conclusion,)-345.1(our)-343.1(study)-345.3(has)-349.9(shown)-346(a)-342.1(clear)-348.9(link)-344.5(between)]TJ -1.0137 -1.1116 TD [(neurogenesis)-609.7(and)-597.7(osteogenesis)-609.6(in)-595.6(hBMSCs)-602.5(and)-603.5(demon-)]TJ T* [(strated)-447.8(that)-443.6(BDNF)-444.8(treatment)-447(can)-443.4(enhance)-444.3(both)-442.3(processes,)]TJ 0 -1.1174 TD [(although)-430.7(the)-425.1(exact)-423.8(mechanism)-430.5(remains)-425.9(unclear.)-429.4(This)-420.2(sug-)]TJ 0 -1.1116 TD [(gests)-392.3(that)-391.7(BDNF)-392.9(may)-397.4(have)-386.9(a)-393.9(future)-393.7(role)-391.6(in)-388.2(improving)-391.5(the)]TJ T* [(outcome)-264.8(for)-256.7(patients)-264.8(requiring)-258.9(bone)-259(tissue)-261.1(engineering,)-266.9(such)]TJ T* [(as)-337.2(after)-336.2(bone)-333.9(augmentation)-335.1(in)-336.4(dental)-337.5(implant)-333(surgery.)]TJ /F8 1 Tf 8.9663 0 0 8.9663 59.7543 151.7669 Tm (Acknowledgments)Tj /F4 1 Tf 9.843 0 0 9.843 69.7323 135.326 Tm [(This)-483.6(work)-483.3(was)-489(supported)-483.3(by)-480.3(grants)-485.7(from)-483.6(the)-482.6(National)]TJ -1.0137 -1.1116 TD [(Natural)-247.3(Science)-242.7(Foundation)-242.7(of)-244.1(China)-244(\(81771045,)-238(81400498\))]TJ T* [(and)-338.5(the)-332.9(Beijing)-332.8(National)-340.7(Science)-334.9(Foundation)-334.8(\(7133255\).)]TJ /F8 1 Tf 8.9663 0 0 8.9663 59.7543 88.0441 Tm [(Disclosure)-336.7(Statement)]TJ /F4 1 Tf 9.843 0 0 9.843 69.7323 71.6031 Tm [(No)-337.1(competing)-336.3(nancial)-334.9(interests)-334.7(exist.)]TJ /F8 1 Tf 8.9663 0 0 8.9663 310.8472 725.7825 Tm (References)Tj /F4 1 Tf 9.2951 0 0 9.2951 315.496 709.7384 Tm [(1.)-500.4(J)12.9(o)0(n)18(e)14(s,)-286(K.)22.6(B.)19.4(,)-292.8(M)12.8(ol)18.6(l)12.6(a)0(n)19.9(o)0(,)-280.8(A)0(.)16.5(V)0(.)22.6(,)-292.8(M)12.8(o)0(r)21.8(c)0(u)19.9(e)0(n)19.9(d)0(e)19.9(,)-292.8(J)12.9(.)0(A)16.5(.)0(,)-280.7(C)0(o)19.3(o)0(p)24.1(e)0(r)17.6(,)-292.8(R)13.4(.)0(R)19.4(.)0(,)]TJ 1.2503 -1.1284 TD [(a)14(n)0(d)-488.2(S)15.3(al)20.5(tz)14.4(m)12.5(a)0(n)19.9(,)-494.1(C)13.4(.)0(L)16.2(.)-494.1(B)13.4(o)0(n)18(e)-492.3(an)19.9(d)-494.2(b)0(r)21.8(a)0(i)20.5(n)0(:)-487.7(a)-492.3(re)17.6(vi)18.6(e)14(w)-495.8(of)-484.5(ne)19.9(ur)21.8(al)20.5(,)]TJ 0 -1.1223 TD [(ho)24.1(rm)22.2(on)18(a)14(l)0(,)-353.4(a)0(n)19.9(d)-360(m)12.5(u)0(s)18.9(c)0(u)19.9(l)12.6(os)18.9(ke)19.9(l)12.6(e)0(t)20.5(a)0(l)-351.6(c)0(o)19.9(n)0(n)24.1(e)0(c)15.7(t)12.6(i)12.6(o)0(n)18(s)12.9(.)-359.9(I)0(o)15.7(w)0(a)-347.6(O)0(r)20.2(t)0(h)18.6(o)0(p)-347.9(J)]TJ /F7 1 Tf 0 -1.1284 TD [(24)24.1(,)]TJ /F4 1 Tf 1.5492 0 TD [(12)24.1(3,)-317.4(20)24.1(04)24.1(.)]TJ -2.7995 -1.1284 TD [(2.)-500.4(S)15.3(e)0(r)17.6(r)0(e)17.6(,)-372.1(C.)19.4(M.)18.8(,)-378.2(F)15.3(ar)17.6(l)12.6(a)0(y)19.9(,)-378.2(D.)22.6(,)-378.2(D)0(e)18.3(l)12.6(m)12.5(a)0(s)14.7(,)-372.1(P.)21.3(D.)16.5(,)-372.1(a)0(n)19.9(d)-378.3(Ch)19.3(e)13.9(n)0(u)18(,)-378.2(C)13.4(.)-378.2(Ev)22.2(i-)]TJ 1.2503 -1.1223 TD [(de)19.9(nc)26(e)-236.1(f)0(o)21.8(r)-228.1(a)-236.1(d)0(e)19.9(n)0(s)25(e)-236.1(a)14(n)0(d)-219.9(i)0(n)18.6(t)12.6(im)19(at)20.5(e)-230(i)0(n)18.6(n)0(e)19.9(r)0(v)21.8(a)0(t)20.5(i)12.6(on)-219.9(of)-222.2(t)12.6(h)0(e)-224.1(b)0(o)24.1(n)0(e)-224.1(t)12.6(is)19.5(s)12.9(u)0(e)19.9(,)]TJ 0 -1.1284 TD -.0145 Tc [(in)-14.5(c)5.4(l)-1.9(u)-14.5(d)3.5(in)-14.5(g)-325.8(g)-14.5(l)4.1(u)-14.5(t)10.2(a)-14.5(m)5.8(a)-14.5(t)6(e)-14.5(-c)-14.5(o)5.4(n)-14.5(t)10.2(a)-14.5(i)6(n)-14.5(i)4.1(n)-14.5(g)-325.8()-14.5(b)6.7(e)-14.5(rs.)-337.8(B)-14.5(o)4.8(n)-14.5(e)]TJ /F7 1 Tf 17.8281 0 TD 0 Tc [(25)18(,)]TJ /F4 1 Tf 1.5553 0 TD [(62)24.1(3,)-311.3(19)18(99)24.1(.)]TJ -20.6337 -1.1223 TD [(3.)-500.4(Mach,)-362.1(D.B.,)-366.7(Rogers,)-365.1(S.D.,)-364.8(Sabino,)-367.3(M.C.,)]TJ /F5 1 Tf 18.5356 0 TD [(et)-363.8(al.)]TJ /F4 1 Tf 2.4885 0 TD [(Origins)-368.8(of)]TJ -19.7737 -1.1284 TD [(skeletal)-413.7(pain:)-418.5(sensory)-414.4(and)-419.4(sympathetic)-413.7(innervation)-419.3(of)-417.4(the)]TJ 0 -1.1223 TD [(mouse)-333(femur.)-332.5(Neuroscience)]TJ /F7 1 Tf 11.7166 0 TD (113,)Tj /F4 1 Tf 2.0798 0 TD [(155,)-336(2002.)]TJ -15.0468 -1.1284 TD [(4.)-500.4(Bjurholm,)-305.6(A.,)-312.9(Kreicbergs,)-311.7(A.,)-312.9(Brodin,)-306.3(E.,)-313.2(and)-309.6(Schultzberg,)]TJ 1.2503 -1.1223 TD [(M.)-597.2(Substance)-594.8(P-)-597.1(and)-602.4(CGRP-immunoreactive)-602.9(nerves)-596.2(in)]TJ 0 -1.1284 TD [(bone.)-334.2(Peptides)]TJ /F7 1 Tf 6.2578 0 TD (9,)Tj /F4 1 Tf 1.0857 0 TD [(165,)-329.9(1988.)]TJ -8.5938 -1.1223 TD -.0252 Tc [(5)-25.2(.)-525.6(Bj)5.7(urho)5.2(lm,)-293.6(A)3.6(.,)-293.6(Krei)5.7(cbergs,)-293.6(A)3.6(.,)-293.6(Tereniu)5.2(s)-.1(,)-293.6(L)3.3(.,)-293.6(Go)5.2(ld)5.2(stein)5.2(,)-293.6(M.,)-293.6(a).9(n)5.2(d)]TJ 1.2503 -1.1284 TD -.0255 Tc [(Sch)4.9(u)-1.2(lt)5.4(zberg,)-415.9(M.)-409.8(Neu)4.9(r)-3.6(o)4.9(p)-1.2(ep)4.9(tid)4.9(e)-420.2(Y)3.3(-,)-415.9(tyro)4.9(sine)-414.1(h)4.9(ydro)4.9(xyl)5.4(ase-)-418.3(an)4.9(d)]TJ 0 -1.1223 TD -.0253 Tc [(v)5.1(a).9(soact)5.6(ive)-615.2(i)-.5(n)5.1(t)-.5(esti)5.6(nal)-616.5(p)5.1(oly)5.1(p)-1(ep)5.1(tid)5.1(e-i)5.6(mmu)5.1(noreacti)5.6(v)-1(e)-615.2(n)-1(erves)-616.2(i)5.6(n)]TJ 0 -1.1284 TD [(b)5.2(o)-.9(n)5.2(e)-236.9(an)5.2(d)-232.7(s)-.1(urroun)5.2(di)5.7(ng)-232.7(ti)5.7(ssues)6(.)-232.6(J)-237.9(Aut)5.7(o)-.9(n)-232.7(N)3.6(erv)-232.7(S)2.3(y)5.2(s)-.1(t)]TJ /F7 1 Tf 18.5478 0 TD -.0243 Tc [(25)6.1(,)]TJ /F4 1 Tf 1.4028 0 TD [(11)6.1(9,)-231.7(19)6.1(88)6.1(.)]TJ -21.2009 -1.1223 TD 0 Tc [(6.)-500.4(Hara-Irie,)-390.2(F.,)-393.5(Amizuka,)-388.2(N.,)-392.2(and)-388.9(Ozawa,)-394.7(H.)-392.1(Immunohisto-)]TJ 1.2503 -1.1284 TD [(chemical)-321.4(and)-327.9(ultrastructural)-323(localization)-326.8(of)-325.9(CGRP-positive)]TJ 0 -1.1223 TD [(nerve)-328.6(bers)-332.5(at)-327.2(the)-333.4(epiphyseal)-329.2(trabecules)-335.7(facing)-328.2(the)-333.4(growth)]TJ 0 -1.1284 TD [(plate)-331.2(of)-338.1(rat)-335.7(femurs.)-331.7(Bone)]TJ /F7 1 Tf 10.6615 0 TD (18,)Tj /F4 1 Tf 1.5858 0 TD [(29,)-335.8(1996.)]TJ -13.4976 -1.1223 TD [(7.)-500.4(Goto,)-367.6(T.,)-368.1(Yamaza,)-372.7(T.,)-368.1(Kido,)-373.7(M.A.,)-367.3(and)-370.6(Tanaka,)-369.2(T.)-374.2(Light-)]TJ 1.2503 -1.1284 TD [(and)-291.3(electron-microscopic)-293.8(study)-292(of)-289.3(the)-290.7(distribution)-293.1(of)-289.3(axons)]TJ 0 -1.1223 TD [(containing)-270.4(substance)-279.9(P)-271.4(and)-273(the)-272.4(localization)-271.9(of)-277.1(neurokinin-1)]TJ 0 -1.1284 TD [(receptor)-335(in)-335.2(bone.)-334.2(Cell)-331.7(Tissue)-340.1(Res)]TJ /F7 1 Tf 14.0587 0 TD (293,)Tj /F4 1 Tf 2.0859 0 TD [(87,)-329.7(1998.)]TJ -17.395 -1.1223 TD [(8.)-500.4(Ramnemark,)-404.5(A.,)-404.4(Nyberg,)-405.5(L.,)-404.7(Lorentzon,)-409.9(R.,)-401.5(Englund,)-405(U.,)]TJ 1.2503 -1.1284 TD [(and)-559.7(Gustafson,)-556.1(Y.)-562.9(Progressive)-558(hemiosteoporosis)-563.3(on)-561.4(the)]TJ 0 -1.1223 TD [(paretic)-557.6(side)-558.4(and)-559.7(increased)-561.8(bone)-553.7(mineral)-559.1(density)-558.2(in)-560.8(the)]TJ 0 -1.1284 TD [(nonparetic)-253.1(arm)-250.5(the)-254.1(rst)-248.3(year)-255.3(after)-251.1(severe)-258.9(stroke.)-250(Osteoporos)]TJ 0 -1.1223 TD (Int)Tj /F7 1 Tf 1.4455 0 TD (9,)Tj /F4 1 Tf 1.0857 0 TD [(269,)-329.9(1999.)]TJ -3.7815 -1.1284 TD [(9.)-500.4(Hayashi,)-387.8(M.,)-389.9(Nakashima,)-391.8(T.,)-386.4(Taniguchi,)-394.8(M.,)-383.8(Kodama,)-394.8(T.,)]TJ 1.2503 -1.1223 TD [(Kumanogoh,)-464.2(A.,)-471.5(and)-462.1(Takayanagi,)-471(H.)-471.4(Osteoprotection)-466.9(by)]TJ 0 -1.1284 TD [(semaphorin)-333.6(3A.)-337.4(Nature)]TJ /F7 1 Tf 9.8747 0 TD (485,)Tj /F4 1 Tf 2.0798 0 TD [(69,)-335.8(2012.)]TJ -13.705 -1.1223 TD -.017 Tc [(1)-17(0)-17(.)-517.5(Fuku)-17(d)13.2(a)-3(,)-236.6(T)-17(.)11.4(,)-242.7(Takeda,)-242.7(S)-1.7(.,)-242.7(Xu,)-242.7(R)-3.6(.,)]TJ /F5 1 Tf 14.0343 0 TD 0 Tc [(e)14(t)-219.1(al)30.8(.)]TJ /F4 1 Tf 2.1591 0 TD -.0166 Tc [(Sema3A)-244(regul)-4(ates)-241.5(bon)-16.6(e)9.4(-)]TJ -14.443 -1.1284 TD [(mass)-333.1(accrual)-327.3(t)-4.1(hrou)-16.7(g)13.5(h)-327.9(sens)-3.8(ory)-327.9(i)-4.1(nnervat)-4.1(io)-16.7(n)13.5(s)2.3(.)-327.8(N)-.1(at)-4.1(ure)]TJ /F7 1 Tf 20.2556 0 TD 0 Tc [(49)30.2(7)18.2(,)]TJ /F4 1 Tf 2.0127 0 TD [(49)30.2(0)18.2(,)]TJ -22.2683 -1.1223 TD -.0182 Tc [(201)-18.2(3)12(.)]TJ -1.7505 -1.1284 TD 0 Tc [(11.)-500.5(Unger,)-466.4(R.E.,)-470.7(Dohle,)-469.6(E.,)-471.8(and)-468.2(Kirkpatrick,)-472(C.J.)-467.9(Improving)]TJ 1.7505 -1.1223 TD [(vascularization)-357.8(of)-356.4(engineered)-355.5(bone)-352.4(through)-356.5(the)-351.7(generation)]TJ 0 -1.1284 TD [(of)-332(pro-angiogenic)-341.4(effects)-340.1(in)-335.2(co-culture)-340.8(systems.)-337.1(Adv)-337.5(Drug)]TJ T* [(Deliv)-334.7(Rev)]TJ /F7 1 Tf 4.5073 0 TD (94,)Tj /F4 1 Tf 1.5858 0 TD [(116,)-329.9(2015.)]TJ -7.8436 -1.1223 TD [(12.)-500.5(Yu,)-374(T.,)-374.2(Liu,)-373.9(Q.,)-380(Jiang,)-375.6(T.,)-374.2(Wang,)-375.2(X.S.,)-377(Yang,)-372.4(Y.Z.,)]TJ /F5 1 Tf 23.5857 0 TD [(et)-376(al.)]TJ /F4 1 Tf -21.8353 -1.1284 TD (Channeled)Tj /F6 1 Tf 4.6842 0 TD (b)Tj /F4 1 Tf .555 0 TD [(-TCP)-396.7(scaffolds)-396.3(promoted)-397(vascularization)-400.5(and)]TJ -5.2392 -1.1223 TD [(bone)-303.7(augmentation)-311.1(in)-304.7(mandible)-306.9(of)-307.6(beagle)-305.7(dogs.)-304.7(Adv)-307(Funct)]TJ 0 -1.1284 TD (Mater)Tj /F7 1 Tf 2.7264 0 TD (26,)Tj /F4 1 Tf 1.5858 0 TD [(6719,)-330(2016.)]TJ -6.0626 -1.1223 TD [(13.)-500.5(Young,)-490.3(H.E.,)-485.8(Duplaa,)-492.2(C.,)-493(Katz,)-491.9(R.,)]TJ /F5 1 Tf 17.3584 0 TD [(et)-491.9(al.)]TJ /F4 1 Tf 2.7386 0 TD (Adult-derived)Tj -18.3465 -1.1284 TD [(stem)-405.4(cells)-409.6(and)-407.2(their)-408.6(potential)-410(for)-407.6(use)-406.3(in)-408.4(tissue)-410.8(repair)-409.8(and)]TJ 0 -1.1223 TD [(molecular)-337.9(medicine.)-335.5(J)-334.7(Cell)-331.7(Mol)-334.6(Med)]TJ /F7 1 Tf 15.5164 0 TD (9,)Tj /F4 1 Tf 1.0857 0 TD [(753,)-329.9(2005.)]TJ -18.3526 -1.1284 TD [(14.)-500.5(Khang,)-317.6(G.,)-319(Kim,)-318.2(H.L.,)-321.1(Hong,)-319.4(M.,)-316.7(Lee,)-315.8(D.)-319(Neurogenesis)-327(of)]TJ 1.7505 -1.1223 TD [(bone)-419.5(marrow-derived)-421(mesenchymal)-424.8(stem)-423.7(cells)-421.8(onto)-420.8(beta-)]TJ 0 -1.1284 TD [(mercaptoethanol-loaded)-382.2(PLGA)-380.6(lm.)-374.5(Cell)-380.5(Tissue)-376.7(Res)]TJ /F7 1 Tf 22.2195 0 TD (347,)Tj /F4 1 Tf -22.2195 -1.1223 TD [(713,)-329.9(2012.)]TJ -1.7505 -1.1284 TD [(15.)-500.5(Lin,)-343.4(R.,)-352.7(Ding,)-343.2(Z.,)-349.8(Ma,)-351.5(H.,)]TJ /F5 1 Tf 12.8084 0 TD [(et)-351.6(al.)]TJ /F4 1 Tf 2.458 0 TD [(In)-344.2(vitro)-349.5(conditioned)-349.8(bone)]TJ -13.5159 -1.1223 TD [(marrow-derived)-329.5(mesenchymal)-333.3(stem)-326.1(cells)-330.4(promote)-329.8(de)-327.8(novo)]TJ 0 -1.1284 TD [(functional)-663.1(enteric)-667.4(nerve)-670.2(regeneration,)-668.7(but)-664.7(not)-664.7(through)]TJ 0 -1.1223 TD [(direct-transdifferentiation.)-342.6(Stem)-336(Cells)]TJ /F7 1 Tf 15.6933 0 TD (33,)Tj /F4 1 Tf 1.5858 0 TD [(3545,)-330(2015.)]TJ -19.0296 -1.1284 TD [(16.)-500.5(Shen,)-398.1(Q.,)-398.3(Yin,)-398(Y.,)-398.3(Xia,)-402.2(Q.J.,)]TJ /F5 1 Tf 14.1258 0 TD [(et)-400.4(al.)]TJ /F4 1 Tf 2.5617 0 TD [(Bone)-399.9(marrow)-401.2(stromal)]TJ -14.937 -1.1223 TD [(cells)-452.3(promote)-457.9(neuronal)-456.6(restoration)-457.3(in)-451(rats)-457(with)-452.3(traumatic)]TJ 0 -1.1284 TD [(brain)-433.6(injury:)-434.7(involvement)-440.9(of)-435.6(GDNF)-435.2(regulating)-443.5(BAD)-435.3(and)]TJ 0 -1.1223 TD [(BAX)-331.6(signaling.)-338.4(Cell)-331.7(Physiol)-337.3(Biochem)]TJ /F7 1 Tf 15.9983 0 TD (38,)Tj /F4 1 Tf 1.5797 0 TD [(748,)-336(2016.)]TJ 9.2951 0 0 9.2951 310.8472 92.5228 Tm [(17.)-500.5(Zhang,)-318(Q.,)-319(Zhao,)-317.8(Y.,)-319(Xu,)-319.1(Y.,)]TJ /F5 1 Tf 13.9063 0 TD [(et)-315(al.)]TJ /F4 1 Tf 2.397 0 TD [(Sodium)-313.8(ferulate)-322.2(and)-321.8(n-)]TJ -14.5528 -1.1223 TD [(butylidenephthalate)-685.2(combined)-685.6(with)-684.1(bone)-681.8(marrow)-687.9(stro-)]TJ 0 -1.1284 TD [(mal)-607.5(cells)-604.8(\(BMSCs\))-614.2(improve)-604.3(the)-607.9(therapeutic)-610.6(effects)-614.5(of)]TJ /F8 1 Tf 8.9663 0 0 8.9663 59.7543 749.7069 Tm [(EFFECT)-338(OF)-337.5(BDNF)-330.2(ON)-334.6(BONE)-335.4(NEUROGENESIS/OSTEOGENESIS)-22070.5(1291)]TJ ET endstream endobj 84 0 obj <>stream /GS1 gs BT /F4 1 Tf 9.2951 0 0 9.2951 78.2929 725.1588 Tm 0 0 0 rg 0 Tc 0 Tw [(angiogenesis)-426.2(and)-425.5(neurogenesis)-429.1(after)-421.8(rat)-427.2(focal)-425.6(cerebral)-430.7(is-)]TJ 0 -1.1223 TD [(chemia.)-335.8(J)-334.7(Transl)-337.2(Med)]TJ /F7 1 Tf 9.2708 0 TD (14,)Tj /F4 1 Tf 1.5797 0 TD [(223,)-336(2016.)]TJ -12.601 -1.1284 TD [(18.)-500.5(Konttinen,)-243.3(Y.,)-239.7(Imai,)-244(S.,)-241.1(and)-236.4(Suda,)-245.6(A.)-239.7(Neuropeptides)-242(and)-242.5(the)]TJ 1.7505 -1.1223 TD [(puzzle)-409.4(of)-399.1(bone)-407.3(remodeling.)-407.1(State)-401.2(of)-405.2(the)-406.6(art.)-402.9(Acta)-406.4(Orthop)]TJ 0 -1.1283 TD (Scand)Tj /F7 1 Tf 2.7813 0 TD (67,)Tj /F4 1 Tf 1.5858 0 TD [(632,)-329.9(1996.)]TJ -6.1175 -1.1223 TD [(19.)-500.5(Lerner,)-455(U.H.,)-448.9(and)-456(Persson,)-454(E.)-447.3(Osteotropic)-456.5(effects)-456(by)-451.6(the)]TJ 1.7505 -1.1284 TD [(neuropeptides)-356.4(calcitonin)-353.3(gene-related)-355.6(peptide,)-356(substance)-353.1(P)]TJ 0 -1.1223 TD [(and)-242.5(vasoactive)-241.9(intestinal)-237.9(peptide.)-246.2(J)-237.1(Musculoskelet)-242.1(Neuronal)]TJ 0 -1.1284 TD (Interact)Tj /F7 1 Tf 3.4034 0 TD (8,)Tj /F4 1 Tf 1.0857 0 TD [(154,)-336(2008.)]TJ -6.2395 -1.1223 TD [(20.)-500.5(Soppet,)-434.4(D.,)-434.9(Escandon,)-431.5(E.,)-435.2(Maragos,)-431(J.,)]TJ /F5 1 Tf 18.4868 0 TD [(et)-437(al.)]TJ /F4 1 Tf 2.6288 0 TD [(The)-433.5(neuro-)]TJ -19.3651 -1.1284 TD [(trophic)-817.6(factors)-817.7(brain-derived)-819.3(neurotrophic)-818.8(factor)-818.4(and)]TJ 0 -1.1223 TD [(neurotrophin-3)-347.5(are)-346.6(ligands)-344.7(for)-346.6(the)-345.6(trkB)-342.6(tyrosine)-347.2(kinase)-349.4(re-)]TJ 0 -1.1284 TD [(ceptor.)-334.4(Cell)]TJ /F7 1 Tf 5.1051 0 TD (65,)Tj /F4 1 Tf 1.5797 0 TD [(895,)-336(1991.)]TJ -8.4352 -1.1284 TD [(21.)-500.5(Barbacid,)-380.2(M.)-377.6(The)-372.5(Trk)-376.7(family)-377.9(of)-380.8(neurotrophin)-375.4(receptors.)-377(J)]TJ 1.7505 -1.1223 TD (Neurobiol)Tj /F7 1 Tf 4.3975 0 TD (25,)Tj /F4 1 Tf 1.5797 0 TD [(1386,)-336.1(1994.)]TJ -7.7277 -1.1284 TD [(22.)-500.5(Kurihara,)-338.6(H.,)-337.3(Shinohara,)-337.7(H.,)-337.3(Yoshino,)-336.7(H.,)-331.2(Takeda,)-338.7(K.,)-337.3(and)]TJ 1.7505 -1.1223 TD [(Shiba,)-324.5(H.)-319(Neurotrophins)-327.4(in)-323(cultured)-327.9(cells)-324.3(from)-321.9(periodontal)]TJ 0 -1.1284 TD [(tissues.)-336.9(J)-334.7(Periodontol)]TJ /F7 1 Tf 8.9781 0 TD (74,)Tj /F4 1 Tf 1.5858 0 TD [(76,)-329.7(2003.)]TJ -12.3144 -1.1223 TD [(23.)-500.5(Takeda,)-491.2(K.,)-483.7(Shiba,)-483.1(H.,)-489.8(Mizuno,)-485.7(N.,)]TJ /F5 1 Tf 17.4194 0 TD [(et)-485.8(al.)]TJ /F4 1 Tf 2.7325 0 TD (Brain-derived)Tj -18.4014 -1.1284 TD [(neurotrophic)-440.6(factor)-440.3(enhances)-438(periodontal)-437.6(tissue)-441.3(regenera-)]TJ 0 -1.1223 TD [(tion.)-335(Tissue)-334(Eng)]TJ /F7 1 Tf 7.0385 0 TD (11,)Tj /F4 1 Tf 1.5858 0 TD [(1618,)-336.1(2005.)]TJ -10.3748 -1.1284 TD [(24.)-500.5(Hutchison,)-511.4(M.R.)-510.7(BDNF)-505.4(alters)-515.8(ERK/p38)-508.8(MAPK)-506(activity)]TJ 1.7505 -1.1223 TD [(ratios)-578.7(to)-573(promote)-573.8(differentiation)-580(in)-573(growth)-571.4(plate)-581.3(chon-)]TJ 0 -1.1284 TD [(drocytes.)-333.8(Mol)-334.6(Endocrinol)]TJ /F7 1 Tf 10.7712 0 TD (26,)Tj /F4 1 Tf 1.5797 0 TD [(1406,)-336.1(2012.)]TJ -14.1014 -1.1223 TD [(25.)-500.5(Hu)22.5(tc)20.5(hi)18.6(s)12.9(o)0(n)18(,)-616.1(M)12.8(.)0(R)19.4(.)0(,)-604(B)0(a)21.2(s)0(s)19.8(e)0(t)20.5(t)12.6(,)-616.1(M)0(.)18.8(H)0(.)22.6(,)-616.1(an)19.9(d)-616.2(W)0(h)19.8(i)12.6(te)20.5(,)-616.1(P)0(.)21.3(C)0(.)-608.8(S)15.3(CF)16.4(,)]TJ 1.7505 -1.1284 TD [(BD)17.8(NF)25.7(,)-274.5(a)0(n)19.9(d)-268.5(Ga)18.3(s6)-261.7(ar)17.6(e)-272.7(r)0(e)23.7(g)0(u)18(l)12.6(at)20.5(or)21.8(s)-273.7(o)0(f)-258.8(g)0(r)21.8(o)0(w)16.4(t)12.6(h)-274.6(p)0(l)24.7(a)0(t)20.5(e)-272.7(ch)19.9(on)18(dr)21.8(oc)19.9(yt)24.7(e)]TJ 0 -1.1223 TD [(pr)21.8(ol)18.6(i)12.6(f)0(e)17.6(r)0(a)23.7(t)0(i)19.2(o)0(n)-463.8(a)0(n)19.9(d)-475.9(di)18.6(ff)19.5(e)14(r)0(e)17.6(n)0(t)18.6(i)12.6(at)20.5(i)12.6(o)0(n)18(.)-475.8(M)12.8(o)0(l)-469.4(E)0(n)22.2(d)0(o)18(c)14(ri)16.3(no)24.1(l)]TJ /F7 1 Tf 20.5483 0 TD [(24)18(,)]TJ /F4 1 Tf 1.7078 0 TD [(19)24.1(3,)]TJ -22.2561 -1.1284 TD [(20)24.1(10)18(.)]TJ -1.7505 -1.1223 TD [(26.)-500.5(K)16.6(a)14(j)18.7(i)12.6(y)18.2(a)14(,)-329.4(M)18.9(.,)-311.2(S)15.3(h)0(i)30.8(b)18.2(a)14(,)-329.4(H)16.6(.)18.2(,)-329.4(F)15.3(u)18.2(j)12.6(i)18.7(t)12.6(a)20.1(,)-329.4(T)16.3(.)0(,)]TJ /F5 1 Tf 15.1139 0 TD -.0147 Tc [(et)-343.6(al.)]TJ /F4 1 Tf 2.3665 0 TD 0 Tc [(B)13.4(r)15.8(a)14(i)18.7(n-)27.9(d)18.2(e)14(r)15.8(i)18.7(ve)32.1(d)-329.5(n)18.2(e)14(u)0(r)27.9(o)18.2(-)]TJ -15.7299 -1.1284 TD -.0161 Tc [(tro)-16.1(p)14.1(h)-16.1(i)14.7(c)-270.5(f)-.3(acto)-16.1(r)-256.6(stimulates)-271.5(bon)-16.1(e)9.9(/)]TJ 11.8508 0 TD -.0141 Tc [(cem)4.5(en)4.1(tu)4.1(m)4.5(-relat)4.6(e)-.1(d)-270.4(p)4.1(ro)4.1(tei)4.6(n)-270.4(g)4.1(e)-.1(n)4.1(e)]TJ -11.8508 -1.1223 TD -.0163 Tc [(expression)-315.3(in)-315.3(cementoblasts.)-315.2(J)-314.4(B)3.2(i)-3.7(ol)-314.7(C)3.2(h)-16.3(e)9.7(m)]TJ /F7 1 Tf 16.8217 0 TD 0 Tc [(28)30.2(3)18.2(,)]TJ /F4 1 Tf 2.0006 0 TD [(1)18.2(6)0(2)30.2(5)18.2(9,)-280.8(20)30.2(0)18.2(8)0(.)]TJ -20.5727 -1.1284 TD [(27.)-500.5(Mizuno,)-424.7(N.,)-428.8(Shiba,)-428.2(H.,)-422.7(Xu,)-428.9(W.P.,)]TJ /F5 1 Tf 16.3581 0 TD [(et)-424.8(al.)]TJ /F4 1 Tf 2.6105 0 TD [(Effect)-430(of)-423.5(neuro-)]TJ -17.2181 -1.1223 TD [(trophins)-257.6(on)-250.4(differentiation,)-262.9(calcication)-261.2(and)-254.7(proliferation)-258.9(in)]TJ 0 -1.1284 TD [(cultures)-314.8(of)-307.6(human)-309.5(pulp)-311.1(cells.)-306(Cell)-313.4(Biol)-309.2(Int)]TJ /F7 1 Tf 17.6085 0 TD (31,)Tj /F4 1 Tf 1.5553 0 TD [(1462,)-311.7(2007.)]TJ -20.9143 -1.1223 TD [(28.)-500.5(Bouler,)-463(J.M.,)-468.5(Pilet,)-463.6(P.,)-466.7(Gauthier,)-463.7(O.,)-465.4(and)-462.1(Verron,)-468.8(E.)-465.6(Bi-)]TJ 1.7505 -1.1284 TD [(phasic)-245.7(calcium)-243.8(phosphate)-246.1(ceramics)-244.1(for)-242.9(bone)-248.8(reconstruction:)]TJ 0 -1.1223 TD [(a)-254.4(review)-262.7(of)-258.8(biological)-257.6(response.)-260.3(Acta)-260.1(Biomater)]TJ /F7 1 Tf 19.2126 0 TD (15,)Tj /F4 1 Tf 1.5065 0 TD [(1,)-256.4(2017.)]TJ -22.4696 -1.1284 TD [(29.)-500.5(Livak,)-354(K.,)-349.5(and)-352.3(Schmittgen,)-352.2(T.D.)-351.6(Analysis)-357.8(of)-350.3(relative)-355.9(gene)]TJ 1.7505 -1.1223 TD [(expression)-272.1(data)-264.6(using)-267.6(real)-273(time)-265.5(quantitative)-273.8(PCR)-269.1(and)-266.9(the)-266.3(2-)]TJ /F6 1 Tf 0 -1.1284 TD (DD)Tj /F4 1 Tf 1.3357 0 TD [(CT)-330.2(method.)-333.5(Methods)]TJ /F7 1 Tf 9.0391 0 TD (25,)Tj /F4 1 Tf 1.5858 0 TD [(402,)-329.9(2001.)]TJ -13.7111 -1.1223 TD [(30.)-500.5(Izant,)-675.8(J.G.,)-672.1(and)-669.5(McIntosh,)-676.5(J.R.)-675.2(Microtubule-associated)]TJ 1.7505 -1.1284 TD [(proteins:)-352.9(a)-352(monoclonal)-356(antibody)-358(to)-347.4(MAP2)-358.1(binds)-353(to)-347.4(differ-)]TJ 0 -1.1223 TD [(entiated)-243.8(neurons.)-244.6(Proc)-247.9(Natl)-243.1(Acad)-248.4(Sci)-244.8(U)-239.6(S)-247(A)]TJ /F7 1 Tf 17.7366 0 TD (77,)Tj /F4 1 Tf 1.4943 0 TD [(4741,)-244.6(1980.)]TJ -20.9814 -1.1284 TD [(31.)-500.5(P)15.3(h)18.2(i)12.6(n)18.2(n)18.2(e)14(y,)-329.6(D)16.6(.)18.2(G)16.6(.)0(,)-329.5(H)16.6(i)18.7(l)12.6(l)18.7(,)-341.6(K.)28.7(,)-341.6(M)18.9(i)12.6(c)14(h)18.2(e)14(l)18.7(s)12.9(o)18.2(n)0(,)-329.6(C)19.5(.,)]TJ /F5 1 Tf 17.7488 0 TD -.0192 Tc [(et)-366.4(al)]TJ /F4 1 Tf 1.7993 0 TD -.0157 Tc [(.)-357.3(B)-2.3(iolo)-15.7(g)14.5(i)-3.1(c)4.4(a)-1.7(l)-356.8(ac-)]TJ -17.7976 -1.1223 TD -.0154 Tc [(tivities)-350.1(encod)-15.4(e)10.6(d)-351(b)2.8(y)-357.1(t)3.3(h)-15.4(e)-343.1(murine)-355.2(mesenchymal)-350.4(stem)-356.7(c)4.7(e)-1.4(ll)-350.4(tran-)]TJ 0 -1.1284 TD 0 Tc [(s)12.9(c)20.1(r)15.8(i)12.6(p)18.2(t)12.6(o)18.2(m)18.6(e)-400.8(p)18.2(r)15.8(o)18.2(vi)30.8(d)18.2(e)-400.8(a)-394.7(b)18.2(a)14(s)12.9(i)18.7(s)-395.7(f)15.8(o)18.2(r)-398.9(t)18.7(he)32.1(i)12.6(r)-392.8(de)32.1(ve)26(l)18.7(o)18.2(pm)30.6(e)14(n)18.2(t)12.6(a)14(l)-389.9(p)0(o)30.2(t)12.6(e)20.1(n)0(t)30.8(i)12.6(a)20.1(l)]TJ T* -.0155 Tc [(and)-332.8(b)2.7(ro)-15.5(a)10.5(d)-332.8(therapeu)-15.5(t)15.3(i)3.2(c)-337(e)-1.5(fc)4.6(acy.)-332.7(S)-.2(te)4.6(m)-338.5(C)4(ells)]TJ /F7 1 Tf 17.1693 0 TD 0 Tc [(24)30.2(,)]TJ /F4 1 Tf 1.537 0 TD -.0182 Tc [(18)-18.2(6)12(,)-335.4(20)-18.2(0)12(6)0(.)]TJ -20.4568 -1.1223 TD 0 Tc [(32.)-500.5(Jaiswal,)-483.9(R.K.,)-476.5(Jaiswal,)-483.9(N.,)-477.6(Bruder,)-484.2(S.P.,)-475.9(Mbalaviele,)-485.5(G.,)]TJ 1.7505 -1.1284 TD [(Marshak,)-418.9(D.R.,)-421.6(and)-419.4(Pittenger,)-415.8(M.F.)-417.3(Adult)-422(human)-419.3(mesen-)]TJ 0 -1.1223 TD [(chymal)-404.7(stem)-405.4(cell)-404.3(differentiation)-403.1(to)-402.3(the)-400.5(osteogenic)-408.5(or)-399.1(adi-)]TJ 0 -1.1284 TD [(pogenic)-399.2(lineage)-396.7(is)-401.4(regulated)-399.3(by)-396.7(mitogen-activated)-400.7(protein)]TJ 0 -1.1223 TD [(kinase.)-337.3(J)-334.7(Biol)-333.6(Chem)]TJ /F7 1 Tf 8.6548 0 TD (275,)Tj /F4 1 Tf 2.0859 0 TD [(9645,)-330(2000.)]TJ -12.4912 -1.1284 TD [(33.)-500.5(De)18.3(hm)24.5(el)20.5(t,)-530.3(L.)22.3(,)-542.9(a)0(n)19.9(d)-536.9(Ha)18.3(l)12.6(p)0(a)19.9(i)0(n)18.6(,)-536.8(S.)-533.7(Th)22.2(e)-541.1(M)12.8(AP)19.6(2/)18.6(Ta)24.1(u)-543(f)0(a)23.7(m)0(i)19(l)12.6(y)-543(o)0(f)]TJ 1.7505 -1.1223 TD [(m)12.5(i)0(c)20.5(r)0(o)21.8(t)0(u)18.6(b)0(u)24.1(l)0(e)14.4(-)15.8(as)14.7(s)12.9(o)0(c)19.9(i)12.6(at)20.5(ed)-291.2(pr)21.8(ot)18.6(e)14(i)0(n)18.6(s)12.9(.)-298.9(G)0(e)18.3(n)0(o)24.1(m)0(e)-290.7(B)13.4(io)18.6(l)]TJ /F7 1 Tf 18.7125 0 TD (6,)Tj /F4 1 Tf 1.0369 0 TD [(20)18(4,)-286.9(20)24.1(05)18(.)]TJ -21.4998 -1.1284 TD [(34.)-500.5(Geisert,)-371.2(E.E.,)-364.1(Jr.,)-367.8(Johnson,)-371.4(H.G.,)-363.5(and)-370.6(Binder,)-365.4(L.I.)-370.6(Expres-)]TJ 1.7505 -1.1223 TD [(sion)-334.6(of)-338.1(microtubule-associated)-345.2(protein)-335.8(2)-335.6(b)0(y)-335.7(reactive)-342.4(astro-)]TJ 9.2951 0 0 9.2951 78.2929 139.3511 Tm [(cytes.)-337.1(Proc)-333.3(Natl)-334.6(Acad)-333.8(Sci)-336.3(U)-337.2(S)-332.4(A)]TJ /F7 1 Tf 13.9246 0 TD (87,)Tj /F4 1 Tf 1.5858 0 TD [(3967,)-330(1990.)]TJ 9.7466 63.0234 TD [(35.)-500.5(Kh)16.4(os)25(la)20.5(,)-384.3(S)0(.)21.3(,)-384.3(We)21.7(st)19.5(en)19.9(do)18(rf)25.6(,)-384.3(J)0(.)19(J)12.9(.,)-378.3(a)14(n)0(d)-372.3(M)0(o)]TJ 16.4008 .0244 TD ()Tj .4086 -.0244 TD [(dd)24.1(er)17.6(,)-384.3(U)0(.)22.6(I)0(.)-374.6(C)0(o)19.3(n)0(c)19.9(i)12.6(s)12.9(e)-388.6(re)23.7(-)]TJ -15.059 -1.1223 TD [(vi)18.6(ew)18.3(:)-322.8(i)0(n)18.6(s)12.9(ig)18.6(ht)18.6(s)-322.5(f)0(r)19.5(o)0(m)-317(n)0(o)24.1(r)0(m)22.2(a)0(l)-321.1(b)0(o)24.1(n)0(e)-315.6(r)0(e)17.6(m)12.5(od)18(e)14(l)0(i)19.2(n)0(g)-317.4(a)0(n)19.9(d)-323.4(st)19.5(em)-315.1(ce)15.7(l)12.6(l)12.6(-)]TJ 0 -1.1284 TD [(ba)19.9(se)20.8(d)-323.4(t)0(h)18.6(e)0(r)23.7(a)0(p)19.9(i)0(e)20.5(s)-322.5(fo)15.7(r)-319.6(b)0(o)18(n)0(e)-309.5(r)0(e)17.6(p)0(a)19.9(i)12.6(r.)-313.6(S)15.3(t)0(e)20.5(m)-323(Ce)15.1(l)12.6(l)12.6(s)]TJ /F7 1 Tf 17.6756 0 TD [(28)18(,)]TJ /F4 1 Tf 1.5553 0 TD [(21)24.1(24)18(,)-323.3(2)0(0)24.1(1)0(0)24.1(.)]TJ -20.9814 -1.1223 TD [(36.)-500.5(Chopp,)-499.6(M.,)-493.6(and)-492.6(Li,)-495.7(Y.)-495.8(Treatment)-504.5(of)-490.5(neural)-499(injury)-496.1(with)]TJ 1.7505 -1.1283 TD [(marrow)-340.2(stromal)-334.4(cells.)-336.5(Lancet)-338.1(Neurol)]TJ /F7 1 Tf 15.4067 0 TD (1,)Tj /F4 1 Tf 1.0857 0 TD [(92,)-329.7(2002.)]TJ -18.2428 -1.1223 TD [(37.)-500.5(Himes,)-254.8(B.T.,)-245(Neuhuber,)-251.4(B.,)-249(Coleman,)-251.2(C.,)]TJ /F5 1 Tf 18.5417 0 TD [(et)-254(al.)]TJ /F4 1 Tf 2.2628 0 TD [(Recovery)-246.6(of)]TJ -19.054 -1.1284 TD [(function)-238.3(following)-241.4(grafting)-240.6(of)-234.4(human)-242.4(bone)-236.6(marrowderived)]TJ 0 -1.1223 TD [(stromal)-541.8(cells)-543.8(into)-536.2(the)-540.8(injured)-537(spinal)-539.8(cord.)-537.8(Neurorehabil)]TJ 0 -1.1284 TD [(Neural)-335.9(Repair)]TJ /F7 1 Tf 6.0748 0 TD (20,)Tj /F4 1 Tf 1.5858 0 TD [(278,)-329.9(2006.)]TJ -9.4111 -1.1223 TD [(38.)-500.5(Kanekiyo,)-333.9(K.,)-337.3(Wakabayashi,)-332.5(T.,)-331.5(Nakano,)-334.2(N.,)]TJ /F5 1 Tf 20.4568 0 TD [(et)-333.3(al)]TJ /F4 1 Tf 1.842 0 TD [(.)-335.5(Effects)]TJ -20.5483 -1.1284 TD [(of)-478.3(intrathecal)-482(injection)-477.1(of)-478.3(the)-473.7(conditioned)-477.9(medium)-479.4(from)]TJ 0 -1.1223 TD [(bone)-364.6(marrow)-364.6(stromal)-364.9(cells)-367(on)-360.1(spinal)-362.9(cord)-360.9(injury)-368(in)-359.6(rats.)-365.6(J)]TJ 0 -1.1284 TD (Neurotrauma)Tj /F7 1 Tf 5.6296 0 TD (35,)Tj /F4 1 Tf 1.5797 0 TD [(521,)-336(2018.)]TJ -8.9598 -1.1284 TD [(39.)-500.5(Gu,)-428.9(Y.,)-428.8(Li,)-428.6(Z.,)-423(Huang,)-433.5(J.,)-426.3(Wang,)-424(H.,)-428.8(Gu,)-428.9(X.,)-428.8(and)-425.5(Gu,)-428.9(J.)]TJ 1.7505 -1.1223 TD [(Application)-619.2(of)-612.5(marrow)-620.8(mesenchymal)-613.8(stem)-618.9(cell-derived)]TJ 0 -1.1284 TD [(extracellular)-269.2(matrix)-268.1(in)-262(peripheral)-267.6(nervetissue)-269.8(engineering.)-265.5(J)]TJ 0 -1.1223 TD [(Tissue)-340.1(Eng)-331.7(Regen)-337.2(Med)]TJ /F7 1 Tf 9.9601 0 TD (11,)Tj /F4 1 Tf 1.5858 0 TD [(2250,)-330(2017.)]TJ -13.2963 -1.1284 TD [(40.)-500.5(Sun,)-290.1(C.Y.,)-293.5(Hu,)-288.6(Y.,)-294.6(Wang,)-289.8(H.F.,)-291.6(He,)-292.8(W.J.,)-290.6(Wang,)-289.8(Y.D.,)-296.4(and)]TJ 1.7505 -1.1223 TD [(Wu,)-389(T.)-380.3(Brain-derived)-391.1(neurotrophic)-385.7(factor)-385.4(inducing)-382.4(angio-)]TJ 0 -1.1284 TD [(genesis)-318.1(through)-313.8(modulation)-308.5(of)-313.7(matrix-degrading)-318.6(proteases.)]TJ 0 -1.1223 TD [(Chin)-334.1(Med)-339.4(J)-328.6(\(Engl\))]TJ /F7 1 Tf 8.0632 0 TD (119,)Tj /F4 1 Tf 2.0859 0 TD [(589,)-329.9(2006.)]TJ -11.8996 -1.1284 TD -.0227 Tc [(4)-22.7(1)-22.7(.)-523.2(U)-6.1(s)2.4(u)-4.5(i)2.1(,)-205.7(T)-.3(.)-4.5(,)-199.6(Nar)-6.9(uo,)-205.7(A.)-4.5(,)-199.6(O)-6.1(kada,)-205.7(M)-3.8(.,)-199.6(H)-6.1(a)-2.6(yab)-4.5(e)3.5(,)-205.7(Y)0(.)-4.5(,)-199.6(an)-4.5(d)-199.7(Y)-6.1(am)-4.1(awak)-4.5(i,)-205.7(H.)]TJ 1.7505 -1.1223 TD [(Brai)-3.9(n-d)-4.4(e)-2.5(ri)-3.9(ved)-437.5(n)1.7(eu)-4.4(rot)-3.9(r)-.7(o)-4.4(phi)-3.9(c)-441.7(f)-.7(acto)-4.4(r)-433.7(p)-4.4(r)-.7(om)-4(ot)-3.9(es)-436.6(an)-4.4(gi)-3.9(og)-4.4(en)-4.4(i)-3.9(c)-435.6(t)-3.9(u)1.7(b)-4.4(e)]TJ 0 -1.1284 TD -.0232 Tc 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