Role of IL-1 beta and prostaglandins in beta 2-microglobulin-induced bone mineral dissolution.
beta 2-microglobulin (beta 2m) induces an osteoclast-mediated net calcium efflux from neonatal mouse calvariae which occurs only after 48 hours of incubation, suggesting that beta 2m acts via other growth factors. To further test this hypothesis, calvariae were incubated with and without beta 2m 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 2m 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 2m in basal medium and that in calvariae incubated with and without beta 2m in indomethacin supplemented medium was similar, suggesting a prostaglandin independent mechanism. There was a time dependent increase in PGE2 in basal medium which was unaffected by beta 2m. 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 2m induced calcium efflux. Anti-IL-1 beta had no effect on the basal release of beta-glucuronidase but partially blocked the beta 2m induced release of beta-glucuronidase. Thus, the beta 2m-induced calcium efflux observed in neonatal mouse calvariae is dependent on interleukin-1 beta but not prostaglandins.
Moe
S M
SM
Indiana University School of Medicine, Indianapolis, USA.
Hack
B K
BK
Cummings
S A
SA
Sprague
S M
SM
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D012886:Skull / Q000378:metabolism; D001613:beta 2-Microglobulin
D007375:Interleukin-1; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D001613:beta 2-Microglobulin; D007213:Indomethacin