ROLE OF IL-1-BETA AND PROSTAGLANDINS IN BETA(2)-MICROGLOBULIN-INDUCED BONE-MINERAL DISSOLUTION

beta 2-microglobulin (beta(2)m) induces an osteoclast-mediated net calcium efflux from neonatal mouse calvariae which occurs only after 48 hours of incubation, suggesting that beta(2)m acts via other growth factors. To further test this hypothesis, calvariae were incubated with and without beta(2)m in the presence of the prostaglandin inhibitor indomethacin, anti-interleukin-1 beta antibody (anti-IL-1 beta), or interleukin-1 beta receptor antagonist (IL-1 beta RA). The addition of beta(2)m to the culture medium stimulated, whereas indomethacin inhibited basal calcium efflux following 48 hours. However, the difference (delta) between the calcium efflux induced in calvariae incubated with and without beta(2)m in basal medium and that in calvariae incubated with and without beta(2)m in indomethacin supplemented medium was similar, suggesting a prostaglandin independent mechanism. There was a time dependent increase in PGE(2) in basal medium which was unaffected by beta(2)m. In contrast, pre-incubating calvariae with either anti-IL-1 beta or IL-1 beta RA did not alter basal calcium efflux but completely blocked the beta(2)m induced calcium efflux. Anti-IL-1 beta had no effect on the basal release of beta-glucuronidase but partially blocked the beta(2)m induced release of beta-glucuronidase. Thus, the beta(2)m-induced calcium efflux observed in neonatal mouse calvariae is dependent on interleukin-1 beta but not prostaglandins.