title: Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.
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.
authors.affiliation: Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan. fvbd7042@mb.infoweb.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: S I
authors.initials: SI
authors.lastname: Mochizuki
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: N
authors.initials: N
authors.lastname: Fujise
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Kuriyama
authors.forename: T
authors.initials: T
authors.lastname: Kanno
authors.forename: A
authors.initials: A
authors.lastname: Murakami
authors.forename: E
authors.initials: E
authors.lastname: Tsuda
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Higashio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat