Cited by 1,201Bone Metabolism and DiseasesBone health and osteoporosis researchBone and Dental Protein Studies

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Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by which OPG/OCIF Inhibits Osteoclastogenesis in Vitro1

Yasuda, Hisataka, Shima, Nobuyuki, Nakagawa, Nobuaki, Mochizuki, Shin-Ichi, Yano, Kazuki, Fujise, Nobuaki, Sato, Yasushi, Goto, Masaaki, Yamaguchi, Kyoji, Kuriyama, Masayoshi, Kanno, Takeshi, Murakami, Akihiko, Tsuda, Eisuke, Morinaga, Tomonori, Higashio, Kanji·1998·Endocrinology

DOI 10.1210/endo.139.3.5837

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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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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
ORCID: Yasuda, Hisataka
Sato, Yasushi
Goto, Masaaki
Kanno, Takeshi
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1998-03
Volume: 139
Issue: 3
Pages: 1329-1337
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.139.3.5837
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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Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by which OPG/OCIF Inhibits Osteoclastogenesis in Vitro1

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