Role of IL-1β and prostaglandins in β2-microglobulin-induced bone mineral dissolution

Role of IL-1β and prostaglandins in β 2 -microglobulin-induced bone mineral dissolution. β 2 -microglobulin (β 2 m) induces an osteoclast-mediated net calcium efflux from neonatal mouse calvariae which occurs only after 48 hours of incubation, suggesting that β 2 m acts via other growth factors. To further test this hypothesis, calvariae were incubated with and without β 2 m in the presence of the prostaglandin inhibitor indomethacin, anti-interleukin-1β antibody (anti-IL-1β), or interleukin-1β receptor antagonist (IL-1β RA). The addition of β 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 β 2 m in basal medium and that in calvariae incubated with and without β 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 β 2 m. In contrast, pre-incubating calvariae with either anti-IL-1β or IL-1βRA did not alter basal calcium efflux but completely blocked the β 2 m induced calcium efflux. Anti-IL-1β had no effect on the basal release of β-glucuronidase but partially blocked the β 2 m induced release of β-glucuronidase. Thus, the β 2 m-induced calcium efflux observed in neonatal mouse calvariae is dependent on interleukin-1β but not prostaglandins.