ROLE OF ENDOGENOUS PGE(2) IN OSTEOBLASTIC FUNCTIONS OF A CLONAL OSTEOBLAST-LIKE CELL, MC3T3-E1

MC3T3-E1 cells actively synthesized and released prostaglandin E2 (PGE 2) during culture. PGE2 release was minimal on day 9 and gradually inc reased with culture up to day 27. DNA content gradually increased unti l day 27. Alkaline phosphatase (ALP) activity increased up to day 15 a nd decreased thereafter. In contrast to the decrease in ALP activity, calcium accumulation increased rapidly after day 21, possibly due to m ineralization by the cells. Indomethacin, a cyclooxygenase inhibitor, blocked PGE, production completely at concentrations higher than 0.3 m umol/L. In the presence of indomethacin (3 mumol/L), DNA content was s lightly decreased on day 27. Furthermore, ALP activity on day 15 was g reater than that of the control and this high activity was maintained until day 27. However, calcium accumulation was not affected by the ad dition of indomethacin. These results suggest that endogenous PGE, dow n-regulates ALP activity and slightly stimulates the proliferation of MC3T3-E1 cells as an autocrine mediator, although it does not directly influence the cells' mineralizing activity.