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Celecoxib inhibits osteoblast differentiation independent of cyclooxygenase activity
Author(s) -
Matsuyama Atsushi,
Higashi Sen,
Tanizaki Saori,
Morotomi Takahiko,
Washio Ayako,
Ohsumi Tomoko,
Kitamura Chiaki,
Takeuchi Hiroshi
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12846
Subject(s) - celecoxib , cyclooxygenase , osteoblast , chemistry , pharmacology , prostaglandin e2 , cell culture , cellular differentiation , endocrinology , medicine , microbiology and biotechnology , biochemistry , biology , enzyme , in vitro , gene , genetics
Summary Non‐steroidal anti‐inflammatory drugs ( NSAID s) exert their effects primarily by inhibiting the activity of cyclooxygenase ( COX ), thus suppressing prostaglandin synthesis. Some NSAID s are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX ‐inhibiting activity. To identify NSAID s with COX ‐independent activity, we examined various NSAID s for their ability to inhibit osteoblastic differentiation using the mouse pre‐osteoblast cell line MC 3T3‐E1. Only celecoxib and valdecoxib strongly inhibited osteoblastic differentiation, and this effect was not correlated with COX ‐inhibiting activity. Moreover, 2,5‐dimethyl ( DM )‐celecoxib, a celecoxib analogue that does not inhibit COX activity, also inhibited osteoblastic differentiation. Celecoxib and DM ‐celecoxib inhibited osteoblastic differentiation induced by bone morphogenetic protein ( BMP )‐2 in C2C12 mouse myoblast cell line. Although celecoxib suppresses the growth of some tumour cells, the viability and proliferation of MC 3T3‐E1 cells were not affected by celecoxib or DM ‐celecoxib. Instead, celecoxib and DM ‐celecoxib suppressed BMP ‐2‐induced phosphorylation of Smad1/5, a major downstream target of BMP receptor. Although it is well known that COX plays important roles in osteoblastic differentiation, these results suggest that some NSAID s, such as celecoxib, have targets other than COX and regulate phospho‐dependent intracellular signalling, thereby modifying bone remodelling.