Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.
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.
Tsuda
E
E
Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan. snowls@tokyo.infoweb.or.jp
Goto
M
M
Mochizuki
S
S
Yano
K
K
Kobayashi
F
F
Morinaga
T
T
Higashio
K
K
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D010281:Parathyroid Hormone; D000135:Acid Phosphatase; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase; D002117:Calcitriol