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 osteoclastic function diminish after several days owing to the calcitonin 'escape phenomenon'. We have previously found a unique cell-surface antigen (Kat1-antigen) expressed on rat osteoclasts. Here we show evidence that, in the presence of calcitonin, the Kat1-antigen is involved in osteoclastogenesis. Treatment of bone marrow cultures for forming osteoclast-like cells with anti-Kat1-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-kappaB) 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, mAb Kat1 induced osteoclast-like cell formation. Our current data suggest that 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 osteoclast lineage appears to contribute to the fine regulation of osteoclastogenesis in vivo. Expression of this cell-surface molecule in cells in the osteoclast lineage may partly explain the mechanism responsible for the escape phenomenon.
Kukita
T
T
Oral Cellular and Molecular Biology, Faculty of Dentistry, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan. kukitat@dent.kyushu-u.ac.jp
Kukita
A
A
Watanabe
T
T
Iijima
T
T
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001854:Bone Marrow Cells; D002116:Calcitonin / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D008562:Membrane Glycoproteins / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D053245:RANK Ligand; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015415:Biomarkers; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D002116:Calcitonin