12-O-tetradecanoylphorbol-13-acetate inhibits osteoclast-like cell differentiation in rat bone marrow cultures by inducing macrophage polykaryons.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) at 10(-9) M stimulated the formation of osteoclast-like multinucleated cells (MNCs) in the presence of 1 alpha,25-dihydroxyvitamin D3 in rat bone marrow cultures. However, at 10(-7) M, it clearly inhibited 1 alpha,25-dihydroxyvitamin D3-dependent osteoclast-like MNC formation at 6 days of culture. In cultures treated with 10(-7) M TPA, numerous MNCs that lack the marker enzyme tartrate-resistant acid phosphatase (TRAP) were formed. These TRAP-negative MNCs had neither receptors for calcitonin nor dentine-resorbing activity. The reactivity of the cells against antirat macrophage antibodies was completely different from that of authentic osteoclasts. These data suggest that TRAP-negative MNCs formed in the presence of 10(-7) M TPA are macrophage polykaryons. Time-course studies showed that 10(-7) M TPA stimulated osteoclast-like MNC formation at 4 days of culture, but these osteoclast-like MNCs were converted to TRAP-negative MNCs. Furthermore, 1-(5-isoquinolinyl-sulfonyl)2-methylpiperazine (H-7), a protein kinase-C inhibitor, inhibited osteoclast-like MNC formation in a dose-dependent fashion. These results suggest that activation of protein kinase-C may play a role in osteoclast differentiation.
Kukita
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Second Department of Anatomy, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Kukita
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A
Hata
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Kurisu
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001862:Bone Resorption; D002116:Calcitonin / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015415:Biomarkers; D002273:Carcinogens; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C008876:phorbol-12,13-didecanoate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002116:Calcitonin; D011493:Protein Kinase C; D000135:Acid Phosphatase; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate