Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.
Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.
复制标题
DOI：
10.1210/endo.139.3.5837
复制
发表时间：
1998-03
期刊：
影响因子：
4.8
通讯作者：
H. Yasuda;N. Shima;N. Nakagawa;S. Mochizuki;K. Yano;N. Fujise;Yasushi Sato;M. Goto;K. Yamaguchi;M. Kuriyama;Takeshi Kanno;A. Murakami;E. Tsuda;T. Morinaga;K. Higashio
中科院分区：
文献类型：
--
作者：
H. Yasuda;N. Shima;N. Nakagawa;S. Mochizuki;K. Yano;N. Fujise;Yasushi Sato;M. Goto;K. Yamaguchi;M. Kuriyama;Takeshi Kanno;A. Murakami;E. Tsuda;T. Morinaga;K. Higashio
骨的形态发生和重塑依赖于形成骨的成骨细胞和吸收骨的破骨细胞的综合活性。我们之前报道过分离出一种名为破骨细胞生成抑制因子（OCIF）的新细胞因子，它可以特异性抑制破骨细胞的发育。在这里，我们报告的人OCIF的互补DNA的克隆。OCIF与骨保护素（OPG）相同，OPG是肿瘤坏死因子受体家族的可溶性成员，可抑制破骨细胞生成。重组人OPG/OCIF特异性作用于骨组织，增加正常大鼠骨密度和骨体积，同时减少活性破骨细胞数量。成骨细胞或骨髓源性基质细胞通过细胞间相互作用支持破骨细胞生成。一类OPG/OCIF的高亲和力结合位点出现在小鼠基质细胞系ST 2上，以响应1，25-二羟维生素D3。阻断结合的抗OPG/OCIF抗体消除了OPG/OCIF的生物活性。当该位点被OPG/OCIF阻断时，ST 2细胞不能支持破骨细胞生成。这些结果表明，这些位点参与了基质细胞和破骨细胞祖细胞之间的细胞间信号传导，OPG/OCIF通过阻断这些位点的信号传导来抑制破骨细胞的生成。
The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.