title: The role of phospholipase A2 in interleukin-1 alpha-mediated inhibition of mineralization of the osteoid formed by fetal rat calvaria cells in vitro.
abstract: 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)
authors.affiliation: MRC Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, Ontario, Canada.
authors.forename: L G
authors.initials: LG
authors.lastname: Ellies
authors.forename: J N
authors.initials: JN
authors.lastname: Heersche
authors.forename: W
authors.initials: W
authors.lastname: Pruzanski
authors.forename: P
authors.initials: P
authors.lastname: Vadas
authors.forename: J E
authors.initials: JE
authors.lastname: Aubin
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000494:pharmacology*; D010011:Osteocytes / Q000187:drug effects / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium