Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.
Abstract
A factor which inhibits osteoclast-like cell formation was found in the conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor, termed osteoclastogenesis inhibitory factor, OCIF, was purified to homogeneity. OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of 120,000. The N-terminus of OCIF is blocked and the determination of internal amino acid sequences revealed that OCIF has no homology to known proteins. OCIF inhibited in a dose-dependent manner osteoclastogenesis elicited through three distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D3, parathyroid hormone, and interleukin-11, respectively, in a dose range of 1 to 40 ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone resorption by mature osteoclasts nor exerts any other biological activities. These data strongly suggest that OCIF is a novel cytokine which specifically inhibits osteoclastogenesis.
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OPG/OCIF suppresses osteoclastogenesis in vitro and also suppresses osteoclast activity, survival, and adhesion to bone surfaces.
“This molecule was referred to as osteoclastogenesis inhibitory factor (OCIF) based on its ability to suppress osteoclastogenesis in vitro (5).OPG/OCIF was shown soon thereafter to also suppress osteoclast activity (7)(8)(9), survival (10,11), and adhesion to bone surfaces (12,13).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [5]
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- Authors
- Tsuda, E., Goto, M., Mochizuki, S.-I., Yano, K., Kobayashi, F., Morinaga, T., & Higashio, K.
- Affiliations
- Megmilk Snow Brand (Japan) (JP)
- Corresponding author
- Tsuda, Eisuke
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 234
- Issue
- 1
- Pages
- 137-142
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2063676540
- Cited by
- 787
- References
- 23
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 18 · 2019: 17 · 2018: 20 · 2017: 14 · 2016: 19 · 2015: 22 · 2014: 19 · 2013: 29 · 2012: 28
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoprotegerin, osteoclastogenesis inhibition, human embryonic lung fibroblasts, homodimer, 1,25-dihydroxyvitamin D3, parathyroid hormone, interleukin-11, bone resorption, conditioned medium
- MeSH terms
- Acid Phosphatase, Animals, Calcitriol, Cell Line, Chromatography, Affinity, Chromatography, High Pressure Liquid, Chromatography, Ion Exchange, Electrophoresis, Polyacrylamide Gel, Fibroblasts, Humans, Molecular Weight, Osteoclasts, Parathyroid Hormone, Serine Endopeptidases, Cytokines, Culture Media, Conditioned, Mice
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