DIFFERENTIAL REGULATION OF PHOSPHOLIPASE-A2 BY CYTOKINES INHIBITING BONE-FORMATION AND MINERALIZATION

Treatment of fetal rat calvarial cells with interleukin-lα, tumor necrosis factor-α, transforming growth factor-β1, or group II phospholipase A2 inhibits the number of bone nodules formed in long-term cultures. These same mediators also inhibit the mineralization of fully developed bone nodules in a time and dose-dependent fashion. The pro-inflammatory cytokines interleukin-α and tumor necrosis factor-α cause a dose-dependent induction of rat calvarial cell phospholipase A2-II mRNA levels, suggesting that their effects on bone formation may be mediated indirectly by activation of this enzyme. In contrast, transforming growth factor-β1, which has more potent effects on bone formation than interleukin-α or tumor necrosis factor-α, supresses basal levels of phospholipase A2-II mRNA, indicating a different mechanism of action for this cytokine. © 1992.