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Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by which OPG/OCIF Inhibits Osteoclastogenesis in Vitro1
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.
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“OPG is an atypical member of the TNF receptor family in that it is a secreted protein with no transmembrane domain and no direct signaling properties (4,6).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [6]
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Metadata
- Authors
- Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S.-I., Yano, K., Fujise, N., Sato, Y., Goto, M., Yamaguchi, K., Kuriyama, M., Kanno, T., Murakami, A., Tsuda, E., Morinaga, T., & Higashio, K.
- Affiliations
- Megmilk Snow Brand (Japan) (JP)
- Corresponding author
- Higashio, Kanji
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-03
- Volume
- 139
- Issue
- 3
- Pages
- 1329-1337
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2167886526
- Cited by
- 1,201
- References
- 33
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 21 · 2023: 15 · 2022: 21 · 2021: 21 · 2020: 29 · 2019: 36 · 2018: 22 · 2017: 38 · 2016: 22 · 2015: 28 · 2014: 36 · 2013: 54 · 2012: 35
- FWCI
- 24.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- osteoprotegerin, osteoclastogenesis inhibition, TNF receptor superfamily, bone remodeling, bone mineral density, stromal cells, osteoblasts, cell-to-cell signaling, 1,25-dihydroxyvitamin D3, bone resorption, gene cloning
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Cloning, Molecular, Glycoproteins, Humans, Male, Molecular Sequence Data, Osteoclasts, Recombinant Proteins, Bone Density, Bone Remodeling, Rats, Sprague-Dawley, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Mice, Rats, Osteoprotegerin
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