PROTEIN-KINASE-C INHIBITOR H-7 BLOCKS EFFECTS OF TUMOR-NECROSIS-FACTOR ON BONE-CELLS

AIM: To study the effects of tumor necrosis factor (TNF),on the neonat al mouse osteoblast-enriched calvarial cells and effects of protein ki nase C (PK C) inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) on the TNF actions. METHODS: [H-3] TdR uptake by the osteoblast s was used to measure cell proliferation. Cellular alkaline phosphatas e (AlP) and tartrate resistant acid phosphatase (trAcP) activities wer e determined spectrophotometrically. RESULTS: TNF (1-100 kU . L(-1)) i nhibited both proliferation and expression of AlP activity, but stimul ated trAcP activity. These TNF-induced actions were blocked by simulta neous addition of H-7 (5 - 20 mu mol . L(-1)). CONCLUSION: TNF has pot ent effects on the osteoblasts, and the blockade of TNF actions by H-7 suggests that TNF exert its effects through PK C.