Fatty acid cyclooxygenase activity stimulated by transforming growth factor-beta in mouse osteoblastic cells (MC3T3-E1).

Prostaglandin (PG)E2, a bone-resorption factor, was released essentially as the sole arachidonate metabolite by an osteogenic cell line cloned from mouse calvaria (MC3T3-E1). Transforming growth factor (TGF)-beta (1 ng/ml) or epidermal growth factor (EGF) (10 ng/ml) markedly stimulated the endogenous PGE2 synthesis in the presence of 5% newborn bovine serum. The serum could not be omitted even if both TGF-beta and EGF were added simultaneously. The PGE2 synthesis started after a 1-h lag phase, and reached a maximum at about 3 h after the addition of TGF-beta. The presence of TGF-beta enhanced the cyclooxygenase activity (arachidonic acid----PGH2) assayed with the microsomes or the immunoprecipitate from the solubilized enzyme. The TGF-beta-stimulated PGE2 synthesis was blocked by translation and transcription inhibitors. Furthermore, Western blot analysis using anti-cyclooxygenase antibody demonstrated a higher level of cyclooxygenase in the TGF-beta-treated cells than in the nontreated cells. These experimental results suggested an induction of cyclooxygenase by TGF-beta as previously reported for EGF (K. Yokota et al. (1986) J. Biol. Chem. 261, 15,410-15,415).