Synthetic octacalcium phosphate (OCP) has a potential to enhance new bone formation and exhibits biodegradable characteristics when implanted in experimentally created bone defects. The precise mechanisms of OCP biodegradation remain unclear, though histological observations have revealed that bone-resorbing osteoclasts appear and resorb implanted OCP. To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro. Coculturing of mouse bone marrow cells and osteoblasts in OCP-coated cell culture plates induced osteoclast differentiation, whereas that did not occur without coating. Further, addition of bone morphogenetic protein-2 significantly increased the number of osteoclasts in the OCP-coated wells. In the presence of OCP, osteoblasts expressed receptor activator of NF-κB ligand (RANKL), an osteoclast differentiation factor. In addition, when half of each culture well was coated with OCP, osteoclasts were formed in both coated and noncoated areas, suggesting that soluble factors mediate osteoclast differentiation induced by OCP. Also, calcium levels in culture medium were significantly decreased in the presence of OCP, while experimental reduction of calcium from 8.0 to 5.0 mg/dL significantly induced RANKL mRNA expression. These results suggest that OCP itself decreases calcium levels around implanted OCP, which induces osteoclast differentiation through RANKL expression by osteoblasts.
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References
1.
OgoseA., HottaT., KawashimaH., KondoN., GuW., KamuraT., EndoN.Comparison of hydroxyapatite and β tricalcium phosphate as bone substitutes after excision of bone tumors. J Biomed Mater Res B Appl Biomater, 72:94. 2005.
2.
PanzavoltaS., TorricelliP., SturbaL., BracciB., GiardinoR., BigiA.Setting properties and in vitro bioactivity of strontium-enriched gelatin-calcium phosphate bone cements. J Biomed Mater Res A, 84:965. 2008.
3.
GinebraM.P., DriessensF.C., PlanellJ.A.Effect of the particle size on the micro and nanostructural features of a calcium phosphate cement: a kinetic analysis. Biomaterials, 25:3453. 2004.
4.
SuzukiO., NakamuraM., MiyasakaY., KagayamaM., SakuraiM.Bone formation on synthetic precursors of hydroxyapatite. Tohoku J Exp Med, 164:37. 1991.
5.
Le NihouannenD., HackingS.A., GbureckU., KomarovaS.V., BarraletJ.E.The use of RANKL-coated brushite cement to stimulate bone remodelling. Biomaterials, 29:3253. 2008.
6.
SikiricM.D., GergelyC., ElkaimR., WachtelE., CuisinierF.J., Furedi-MilhoferH.Biomimetic organic-inorganic nanocomposite coatings for titanium implants. J Biomed Mater Res A, 89:759. 2009.
7.
SasanoY., KamakuraS., NakamuraM., SuzukiO., MizoguchiI., AkitaH., KagayamaM.Subperiosteal implantation of octacalcium phosphate (OCP) stimulates both chondrogenesis and osteogenesis in the tibia, but only osteogenesis in the parietal bone of a rat. Anat Rec, 242:40. 1995.
8.
KamakuraS., SasanoY., HommaH., SuzukiO., KagayamaM., MotegiK.Implantation of octacalcium phosphate (OCP) in rat skull defects enhances bone repair. J Dent Res, 78:1682. 1999.
MiyatakeN., KishimotoK.N., AnadaT., ImaizumiH., ItoiE., SuzukiO.Effect of partial hydrolysis of octacalcium phosphate on its osteoconductive characteristics. Biomaterials, 30:1005. 2009.
11.
KikawaT., KashimotoO., ImaizumiH., KokubunS., SuzukiO.Intramembranous bone tissue response to biodegradable octacalcium phosphate implant. Acta Biomaterialia, 5:1756. 2009.
KikuchiM., ItohS., IchinoseS., ShinomiyaK., TanakaJ.Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. Biomaterials, 22:1705. 2001.
ImaizumiH., SakuraiM., KashimotoO., KikawaT., SuzukiO.Comparative study on osteoconductivity by synthetic octacalcium phosphate and sintered hydroxyapatite in rabbit bone marrow. Calcif Tissue Int, 78:45. 2006.
19.
OkudaT., IokuK., YonezawaI., MinagiH., GondaY., KawachiG., KamitakaharaM., ShibataY., MurayamaH., KurosawaH., IkedaT.The slow resorption with replacement by bone of a hydrothermally synthesized pure calcium-deficient hydroxyapatite. Biomaterials, 29:2719. 2008.
20.
OkudaT., IokuK., YonezawaI., MinagiH., KawachiG., GondaY., MurayamaH., ShibataY., MinamiS., KamihiraS., KurosawaH., IkedaT.The effect of the microstructure of β-tricalcium phosphate on the metabolism of subsequently formed bone tissue. Biomaterials, 28:2612. 2007.
21.
HondaY., AnadaT., KamakuraS., MorimotoS., KuriyagawaT., SuzukiO.The effect of microstructure of octacalcium phosphate on the bone regenerative property. Tissue Eng Part A, 15:1965. 2009.
22.
ToyaH., ItoA., FujimoriH., GotoS., IokuK.In vitro estimation of calcium phosphate with pH-controlled simulated body fluid. Trans Mater Res Soc Jpn, 26:1247. 2001.
23.
SuzukiO., NakamuraM., MiyasakaY., KagayamaM., SakuraiM.Maclura pomifera agglutinin-binding glycoconjugates on converted apatite from synthetic octacalcium phosphate implanted into subperiosteal region of mouse calvaria. Bone Miner, 20:151. 1993.
24.
BanS., JindeT., HasegawaJ.Phase transformation of octacalcium phosphate in vivo and in vitro. Dent Mater J, 11:130. 1992.
25.
DekkerR.J., de BruijnJ.D., StigterM., BarrereF., LayrolleP., van BlitterswijkC.A.Bone tissue engineering on amorphous carbonated apatite and crystalline octacalcium phosphate-coated titanium discs. Biomaterials, 26:5231. 2005.
26.
LeGerosR.Z., DaculsiG., OrlyI., AbergasT., TorresW.Solution-mediated transformation of octacalcium phosphate (OCP) to apatite. Scanning Microsc, 3:129. 1989.
27.
TomazicB.B., TungM.S., GregoryT.M., BrownW.E.Mechanism of hydrolysis of octacalcium phosphate. Scanning Electron Microsc, 3:119. 1989.
28.
IijimaM., TohdaH., SuzukiH., YanagisawaT., MoriwakiY.Effects of F- on apatite-octacalcium phosphate intergrowth and crystal morphology in a model system of tooth enamel formation. Calcif Tissue Int, 50:357. 1992.
29.
TungM.S., TomazicB., BrownW.E.The effects of magnesium and fluoride on the hydrolysis of octacalcium phosphate. Arch Oral Biol, 37:585. 1992.
30.
SuzukiO., YagishitaH., YamazakiM., AobaT.Adsorption of bovine serum albumine onto octacalcium phosphate and its hydrolyzates. Cells Mater, 5:45. 1995.
31.
SuzukiO., KamakuraS., KatagiriT.Surface chemistry and biological responses to synthetic octacalcium phosphate. J Biomed Mater Res B Appl Biomater, 77:201. 2006.
32.
AnadaT., KumagaiT., HondaY., MasudaT., KamijoR., KamakuraS., YoshiharaN., KuriyagawaT., ShimauchiH., SuzukiO.Dose-dependent osteogenic effect of octacalcium phosphate on mouse bone marrow stromal cells. Tissue Eng Part A, 14:965. 2008.
33.
KamakuraS., SasanoY., Homma-OhkiH., NakamuraM., SuzukiO., KagayamaM., MotegiK.Multinucleated giant cells recruited by implantation of octacalcium phosphate (OCP) in rat bone marrow share ultrastructural characteristics with osteoclasts. J Electron Microsc (Tokyo), 46:397. 1997.
34.
NasuT., TakemotoM., AkiyamaN., FujibayashiS., NeoM., NakamuraT.EP4 agonist accelerates osteoinduction and degradation of β-tricalcium phosphate by stimulating osteoclastogenesis. J Biomed Mater Res A, 89:601. 2009.
35.
OnishiE., FujibayashiS., TakemotoM., NeoM., MaruyamaT., KokuboT., NakamuraT.Enhancement of bone-bonding ability of bioactive titanium by prostaglandin E2 receptor selective agonist. Biomaterials, 29:877. 2008.
36.
SuzukiO., YagishitaH., AmanoT., AobaT.Reversible structural changes of octacalcium phosphate and labile acid phosphate. J Dent Res, 74:1764. 1995.
37.
TakahashiN., AkatsuT., UdagawaN., SasakiT., YamaguchiA., MoseleyJ.M., MartinT.J., SudaT.Osteoblastic cells are involved in osteoclast formation. Endocrinology, 123:2600. 1988.
38.
DoiY., IwanagaH., ShibutaniT., MoriwakiY., IwayamaY.Osteoclastic responses to various calcium phosphates in cell cultures. J Biomed Mater Res, 47:424. 1999.
39.
AsagiriM., TakayanagiH.The molecular understanding of osteoclast differentiation. Bone, 40:251. 2007.
KongY.Y., YoshidaH., SarosiI., TanH.L., TimmsE., CapparelliC., MoronyS., Oliveira-dos-SantosA.J., VanG., ItieA., KhooW., WakehamA., DunstanC.R., LaceyD.L., MakT.W., BoyleW.J., PenningerJ.M.OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature, 397:315. 1999.
42.
TakamiM., TakahashiN., UdagawaN., MiyauraC., SudaK., WooJ.T., MartinT.J., NagaiK., SudaT.Intracellular calcium and protein kinase C mediate expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin in osteoblasts. Endocrinology, 141:4711. 2000.
43.
O'BrienC.A., LinS.C., BellidoT., ManolagasS.C.Expression levels of gp130 in bone marrow stromal cells determine the magnitude of osteoclastogenic signals generated by IL-6-type cytokines. J Cell Biochem, 79:532. 2000.
44.
TakamiM., WooJ.T., TakahashiN., SudaT., NagaiK.Ca2+-ATPase inhibitors and Ca2+-ionophore induce osteoclast-like cell formation in thecocultures of mouse bone marrow cells and calvarial cells. Biochem Biophys Res Commun, 237:111. 1997.
45.
ChangW., TuC., ChenT.H., BikleD., ShobackD.The extracellular calcium-sensing receptor (CaSR) is a critical modulator of skeletal development. Sci Signal, 1:ra1. 2008.
46.
LamkinM.S., ColclasureC., RodrickM., TroxlerR.F., OffnerG.D., LloydW.S., SchmidK., NimbergR.B.Three forms of BRP-2 (bone resorptive proteins) from human cancer ascites fluid and their relationship to human serum alpha-2 HS-glycoprotein. Calcif Tissue Int, 41:171. 1987.
47.
TsengY.H., MouC.Y., ChanJ.C.Solid-state NMR study of the transformation of octacalcium phosphate to hydroxyapatite: a mechanistic model for central dark line formation. J Am Chem Soc, 128:6909. 2006.
48.
SuzukiO., ImaizumiH., KamakuraS., KatagiriT.Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization. Curr Med Chem, 15:305. 2008.
KoideM., MuraseY., YamatoK., NoguchiT., OkahashiN., NishiharaT.Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1alpha through upregulation of osteoclast differentiation factor and cyclooxygenase-2. Biochem Biophys Res Commun, 259:97. 1999.
51.
UsuiM., XingL., DrissiH., ZuscikM., O'KeefeR., ChenD., BoyceB.F.Murine and chicken chondrocytes regulate osteoclastogenesis by producing RANKL in response to BMP2. J Bone Miner Res, 23:314. 2008.
52.
ItohK., UdagawaN., KatagiriT., IemuraS., UenoN., YasudaH., HigashioK., QuinnJ.M., GillespieM.T., MartinT.J., SudaT., TakahashiN.Bone morphogenetic protein 2 stimulates osteoclast differentiation and srvival supported by receptor activator of nuclear factor-κB ligand. Endocrinology, 142:3656. 2001.
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