TY - JOUR
T1 - 12-o-tetradecanoylphorbol-13-acetate inhibits osteoclast-like cell differentiation in rat bone marrow cultures by inducing macrophage polykaryons
AU - Kukita, Toshio
AU - Kukita, Akiko
AU - Hata, Kazuhiko
AU - Kurisu, Kojiro
PY - 1992/2
Y1 - 1992/2
N2 - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) at 10-9M stimulated the formation of osteoclast-like multinucleated cells (MNCs) in the presence of 1 alpha, 25-dihydroxyvitamin D3in rat bone marrow cultures. However, at 10-7M, it clearly inhibited 1 α, 25-dihydroxyvitamin D3-dependent osteoclast-like MNC formation at 6 days of culture. In cultures treated with 10-7M 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 10-7M TPA are macrophage polykaryons. Time-course studies showed that 10-7M 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.
AB - The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) at 10-9M stimulated the formation of osteoclast-like multinucleated cells (MNCs) in the presence of 1 alpha, 25-dihydroxyvitamin D3in rat bone marrow cultures. However, at 10-7M, it clearly inhibited 1 α, 25-dihydroxyvitamin D3-dependent osteoclast-like MNC formation at 6 days of culture. In cultures treated with 10-7M 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 10-7M TPA are macrophage polykaryons. Time-course studies showed that 10-7M 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.
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U2 - 10.1210/endo.130.2.1310276
DO - 10.1210/endo.130.2.1310276
M3 - Article
C2 - 1310276
AN - SCOPUS:0026577369
VL - 130
SP - 577
EP - 534
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 2
ER -