Osteoclast differentiation antigen, distinct from receptor activator of nuclear factor kappa B, is involved in osteoclastogenesis under calcitonin-regulated conditions

Although calcitonin has been clinically utilized as a primary treatment for several metabolic bone diseases, its inhibitory effects against osteoclast ic function diminish after several days owing to the calcitonin 'escape phe nomenon'. We have previously found a unique cell-surface antigen (Kat1-anti gen) expressed on rat osteoclasts. Here we show evidence that, in the prese nce of calcitonin, the Kat1-antigen is involved in osteoclastogenesis. Trea tment of bone marrow cultures for forming osteoclast-like cells with anti-K at1-antigen monoclonal antibody (mAb Kat1) provoked a marked stimulation of osteoclast-like cell formation only in the presence of calcitonin but not in its absence. Osteoclastogenesis stimulated by the receptor activator of nuclear factor kappa B (NF-KB) ligand/osteoclast differentiation factor was further augmented by mAb Kat1 in the presence of calcitonin. Furthermore, even in the presence of the osteoprotegerin/osteoclast inhibitory factor, m Ab Kat1 induced osteoclast-like cell formation. Our current data suggest th at the Kat1-antigen is a molecule that is distinct from receptor activator of NF-kappaB. The presence of the unique Kat1-antigen on cells in the osteo clast lineage appears to contribute to the fine regulation of osteoclastoge nesis in vivo. Expression of this cell-surface molecule in cells in the ost eoclast lineage may partly explain the mechanism responsible for the escape phenomenon.