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Journal of Dental Research, Vol 72, 18-24, Copyright © 1993 by International & American Associations for Dental Research Online Journals

ARTICLES

The role of phospholipase A2 in interleukin-1 alpha-mediated inhibition of mineralization of the osteoid formed by fetal rat calvaria cells in vitro

L. G. Ellies, J. N. Heersche, W. Pruzanski, P. Vadas and J. E. Aubin
MRC Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, Ontario, Canada.

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-1 alpha or IL-1 beta 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-1 alpha on the mineralization process were examined by the addition of IL-1 alpha 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-1 alpha 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-1 alpha-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-1 alpha-mediated inhibition, suggesting the presence of other mechanisms of exogenous PLA2 action in inhibiting mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)


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