Interleukin-1 (IL-1) may be an important mediator of bone remodeling, since it is a potent stimulator of bone resorption and has biphasic effects on bone formation. Continuous exposure of fetal rat calvaria (RC) cells to IL-la or IL-1β results in a dose-dependent inhibition of both bone nodule formation and mineralization of the organic matrix. In this study, the effects of recombinant human IL-1α on the mineralization process were examined by the addition of IL-la late in the culture period, after osteoid nodules had formed and when they were induced to mineralize by the addition of organic phosphate. By means of a quantitative 45calcium radiolabeling assay, it was shown that short-duration exposures of fully-formed bone nodules to IL-la also inhibited mineralization, and that the duration of treatment directly correlated with the degree of inhibition. Because our earlier studies had demonstrated that IL-1 stimulated the release of PLA2 and PGE2 from RC cells, the effects of PLA2 and of inhibition of PGE2 synthesis on mineralization were investigated. Exogenous Naja naja group I PLA2 had little effect on the mineralization of bone nodules; however, Crotalus adamanteus group II PLA2 inhibited mineralization at concentrations similar to those found in the media from IL-la-treated cultures. Although PLA2 is thought to stimulate PGE2 synthesis by releasing arachidonic acid from membrane phospholipids, PGE2 release by RC cells accounted for only part of the IL-la-mediated inhibition, suggesting the presence of other mechanisms of exogenous PLA2 action in inhibiting mineralization. These results suggest that the IL-1-induced synthesis and release of PLA 2 from RC cells is primarily responsible for the inhibition ofmineralization seen in vitro with exposure to IL-1. Thus, the presence of IL-la in vivo at sites of chronic inflammation or infection may compromise tissue repair by inhibiting bone formation and mineralization as well as stimulating bone resorption.
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