Cyclooxygenase inhibitors enhance cell growth in an osteoblastic cell line, MC3T3‐E1

To elucidate the significance of endogenous prostaglandin E 2 (PGE 2 ) in osteoblastic cell function, we studied the effects of cyclooxygenase inhibitors on cell growth and alkaline phosphatase (ALP) activity in MC3T3‐E1 cells. UMR‐106 cells were also used as references in our experiments. MC3T3‐E1 cells, cultured in α‐minimal essential medium containing 10% fetal bovine serum, were shown to produce PGE 2 , which was markedly suppressed in the presence of indomethacin. Addition of indomethacin resulted in an increase in DNA content and [ 3 H]thymidine incorporation. A similar growth stimulatory effect was observed when structurally different cyclooxygenase inhibitors, that is, acetyl salicylic acid (ASA), flurbiprofen, and piroxicam, were added. These cyclooxygenase inhibitors, however, differed in their effects on ALP activity. Indomethacin and ASA enhanced ALP activity, whereas flurbiprofen and piroxicam suppressed it. We then examined the effects of exogenous addition of PGE 2 . Although exogenous PGE 2 at 6 × 10 −6 M slightly stimulated cell growth, it inhibited cell growth at 6 × 10 −8 M and 6 × 10 −7 M. ALP activity was reduced in a dose‐dependent fashion by exogenous PGE 2 . These results suggest that PGE 2 produced by MC3T3‐E1 may be suppressing cell proliferation and that cyclooxygenase inhibitors, per se, may stimulate cell growth by inhibiting endogenous PGE 2 production in MC3T3‐E1 cells. UMR‐106 cells also produced PGE 2 , although less than MC3T3‐E1 cells. In UMR‐106 cells, the cyclooxygenase inhibitors did not influence DNA content or ALP activity as distinctly as in MC3T3‐E1 cells. DNA content in these cells was reduced only by a high concentration of exogenous PGE 2 (6 × 10 −6 M), and ALP activity was unaltered by exogenous PGE 2 . Thus, although endogenous prostaglandins had a growth inhibitory effect on UMR‐106 cells similar to those on MC3T3‐E1 cells, its role may be less important in UMR‐106 cells.