Transforming Growth Factor-β1 Regulation of Prostaglandin G/H Synthase-2 Expression in Osteoblastic MC3T3-E1 Cells1

Transforming growth factor-β (TGFβ) plays an important role in bone development and remodeling. TGFβ stimulates PGE2 production, enhances interleukin-1-stimulated PGE2 production, and can stimulate PG-mediated bone resorption. We found that TGFβ induced prostaglandin G/H synthase (PGHS-2) messenger RNA (mRNA) and PGE2 production in neonatal mouse calvarial cultures and in primary cells derived from these calvariae. We used MC3T3-E1 cells, an immortalized osteoblastic cell line derived from mouse calvariae, to examine the mechanism of PGHS-2 induction. PGHS-2 mRNA was rapidly induced by TGFβ (10 ng/ml) in MC3T3-E1 cells; mRNA levels peaked at 4–8 h and were still elevated at 24 h. Induction of PGHS-2 protein and PGE2 production correlated with PGHS-2 mRNA levels. In contrast, TGFβ had much less effect on PGHS-1 mRNA levels. Unlike the response to other agonists, PGHS-2 mRNA induction by TGFβ was not enhanced by cycloheximide pretreatment, suggesting a requirement for new protein synthesis. To study transcr...