ISOLATION OF A NOVEL CYTOKINE FROM HUMAN FIBROBLASTS THAT SPECIFICALLY INHIBITS OSTEOCLASTOGENESIS

A factor which inhibits osteoclast-like cell formation was found in th e conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor, termed osteoclastogenesis inhibitory factor, OCIF, was purifie d 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 reveal ed that OCIF has no homology to known proteins. OCIF inhibited in a do se-dependent manner osteoclastogenesis elicited through three distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D-3, pa rathyroid hormone, and interleukin-11, respectively, in a dose range o f 1 to 40 ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone reso rption by mature osteoclasts nor exerts any other biological activitie s. These data strongly suggest that OCIF is a novel cytokine which spe cifically inhibits osteoclastogenesis. (C) 1997 Academic Press.