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Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., 519 Ishibashi-machi, Shimotsuga-gun, Tochigi, 3290512, Japan
Address all correspondence and requests for reprints to: Hisataka Yasuda, Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., 519 Ishibashi-machi, Shimotsuga-gun, Tochigi, 3290512, Japan. E-mail: fvbd7042{at}mb.infoweb.or.jp
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.
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M. Schoppet, K. T. Preissner, and L. C. Hofbauer RANK Ligand and Osteoprotegerin: Paracrine Regulators of Bone Metabolism and Vascular Function Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 549 - 553. [Abstract] [Full Text] [PDF] |
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S. Ito, K. Wakabayashi, O. Ubukata, S. Hayashi, F. Okada, and T. Hata Crystal Structure of the Extracellular Domain of Mouse RANK Ligand at 2.2-A Resolution J. Biol. Chem., February 15, 2002; 277(8): 6631 - 6636. [Abstract] [Full Text] [PDF] |
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M. Haberland, A. F. Schilling, J. M. Rueger, and M. Amling Brain and Bone: Central Regulation of Bone Mass : A New Paradigm in Skeletal Biology J. Bone Joint Surg. Am., December 1, 2001; 83(12): 1871 - 1876. [Full Text] [PDF] |
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A. R. Pettit, H. Ji, D. von Stechow, R. Muller, S. R. Goldring, Y. Choi, C. Benoist, and E. M. Gravallese TRANCE/RANKL Knockout Mice Are Protected from Bone Erosion in a Serum Transfer Model of Arthritis Am. J. Pathol., November 1, 2001; 159(5): 1689 - 1699. [Abstract] [Full Text] [PDF] |
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U Feige Osteoprotegerin Ann Rheum Dis, November 1, 2001; 60(90003): iii81 - 84. [Full Text] [PDF] |
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J. M. Brown, R. L. Vessella, P. J. Kostenuik, C. R. Dunstan, P. H. Lange, and E. Corey Serum Osteoprotegerin Levels Are Increased in Patients with Advanced Prostate Cancer Clin. Cancer Res., October 1, 2001; 7(10): 2977 - 2983. [Abstract] [Full Text] [PDF] |
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G. D. Roodman Biology of Osteoclast Activation in Cancer J. Clin. Oncol., August 1, 2001; 19(15): 3562 - 3571. [Abstract] [Full Text] [PDF] |
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