Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
권호 표지

High extracellular $Ca^{2+}$ alone stimulates osteoclast formation but inhibits in the presence of other osteoclastogenic factors

Shin, Myung-Mi;Kim, Yong-Hee;Kim, Si-Nae;Kim, Gwan-Shik;Baek, Jeong-Hwa

  • Published : 2003.06.30
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Abstract

High ambient $Ca^{2+}$ at bone resorption sites have been implicated to play an important role in the regulation of bone remodeling. The present study was performed to clarify the mode of high extracellular $Ca^{2+}\;({Ca^{2+}}_e)$-induced modulation of osteoclastogenesis and the expression of receptor activator of nuclear factor-${\kappa}$B ligand (RANKL) and osteoprotegerin (OPG), thereby to define its role in osteoclast formation. Mouse bone marrow cells were cocultured with osteoblastic cells in the absence or presence of osteoclastogenic factors such as 1,$25-dihydroxyvitaminD_3\;(1,25-(OH)_2vitD_3)$ and macrophage colony-stimulating factor/soluble RANKL. $Ca^{2+}$ concentration in media (1.8 mM) was adjusted to 3, 5, 7 or 10 mM. Osteoclast formation was confirmed by the appearance of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and the expression of osteoclast phenotypic markers (calcitonin receptor, vitronectin receptor, cathepsin K, matrix metalloproteinase-9, carbonic anhydrase 2). High ${Ca^{2+}}_e$ alone significantly stimulated osteoclast formation in a dose-dependent manner. However, in the presence of highly osteoclastogenic factors, high ${Ca^{2+}}_e$ significantly inhibited osteoclastogenesis. High ${Ca^{2+}}_e$ alone continuously up-regulated RANKL expression while only transiently increased OPG expression. However, in the presence of 1,$25-(OH)_2vitD_3$, high ${Ca^{2+}}_e$ did not change the 1,$25-(OH)_2vitD_3$-induced RANKL expression while increased OPG expression. Taken together, these findings suggest that high ${Ca^{2+}}_e$ alone increase osteoclastogenesis but inhibit in the presence of other osteoclastogenic factors. In addition, high ${Ca^{2+}}_e$-induced osteoclastogenesis may be mediated by osteoblasts via up-regulation of RANKL expression. Meanwhile up-regulated OPG might participate in the inhibitory effect of high ${Ca^{2+}}_e$ on 1,$25-(OH)_2vitD_3$-induced osteoclastogenesis.

Keywords

References

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