Effects of Nonsteroidal Anti-Inflammatory Drugs on Transforming Growth Factor-β Expression and Bioactivity in Rat Osteoblast-Enriched Cultures

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress bone remodeling in normal and repaired bones. Our previous results indicated that ketorolac and indomethacin suppressed proliferation, stimulated early differentiation, and induced apoptosis in cultured osteoblasts. Transforming growth factor-beta (TGF-beta) has been reported to enhance proliferation, suppress differentiation, and prevent apoptosis in osteoblasts. We proposed that one pathway of NSAID effects on osteoblast function might be through inhibition of the expression and/or bioactivity of TGF-beta in osteoblasts. We tested the effects of ketorolac and indomethacin on the expression of TGF-beta1 mRNA and protein and the bioactivity of TGF-beta in osteoblast-enriched cultures derived from fetal calvaria. The effects of prostaglandin E1 (PGE1) and PGE2 on TGF-beta expression and bioactivity were also examined in order to understand more about the role of prostaglandins in osteoblast function. Simultaneously, we estimated whether these NSAID effects on osteoblasts were prostaglandin-related. The results showed that 24-hour treatments with both PGEs and theoretic therapeutic concentrations of ketorolac and indomethacin had no significant effects on the levels of either transcription or translation of TGF-beta or the post-translational function of TGF-beta in osteoblasts. These results suggest that NSAIDs do not affect osteoblast function through changes in TGF-beta action in osteoblasts.