Regular ArticleIsolation 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 1α,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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1α,25(OH)2D3, 1α,25-dihydroxyvitamin D3PTH, parathyroid hormone; TRAP, tartaric acid-resistant acid phosphatase; CHAPS, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate; CT, calcitonin;
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F. L. CoeM. J. Favus, Eds.
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These authors contributed equally to this work.
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To whom correspondence should be addressed. Fax: +81(0285)53-1314. E-mail: [email protected].