RRC ID 39131
Author Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K.
Title Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.
Journal Endocrinology
Abstract 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.
Volume 139(3)
Pages 1329-37
Published 1998-3-1
DOI 10.1210/endo.139.3.5837
PMID 9492069
MeSH Amino Acid Sequence Animals Bone Density / drug effects Bone Remodeling Cells, Cultured Cloning, Molecular Glycoproteins / genetics Glycoproteins / physiology* Humans Male Mice Molecular Sequence Data Osteoclasts / drug effects Osteoclasts / physiology* Osteoprotegerin Rats Rats, Sprague-Dawley Receptors, Cytoplasmic and Nuclear* Receptors, Tumor Necrosis Factor / genetics Receptors, Tumor Necrosis Factor / physiology* Recombinant Proteins / pharmacology
IF 3.934
Times Cited 944
WOS Category ENDOCRINOLOGY & METABOLISM
Resource
Human and Animal Cells MC3T3-E1(RCB1126) ST2(RCB0224)