Prostaglandin E2 stimulates osteoclast formation via endogenous IL-1 beta expressed through protein kinase A.
The present study was conducted to determine whether endogenous IL-1 is involved as a potent mediator of PGE2-stimulated osteoclast formation in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3)-primed calvarial cells from mouse embryos. PGE2 induced IL-1 beta gene expression in the primed calvarial cells. IL-1 beta gene expression was also induced in a dose-dependent manner by forskolin and dibutyryl cAMP. PGE2-induced IL-1 beta gene expression was markedly inhibited by H-89, a potent inhibitor of protein kinase A. On the other hand, osteoclast formation in 1 alpha,25-(OH)2D3-primed calvarial cells was also stimulated by forskolin and dibutyryl cAMP, and their stimulatory effects were dose dependent. H-89 also inhibited PGE2-stimulated osteoclast formation. The presence of the IL-1 beta gene product in the conditioned medium of 1 alpha,25-(OH)2D3-primed calvarial cells treated with PGE2 was proved by the results of an immunoprecipitation assay using anti-mouse IL-1 beta Ab. The addition of anti-mouse IL-1 beta Ab to 1 alpha,25-(OH)2D3 primed calvarial cell cultures markedly inhibited PGE2-stimulated osteoclast formation. The stimulatory effect of conditioned medium of primed calvarial cells treated with PGE2 on osteoclast formation was also inhibited by anti-IL-1 beta Ab pretreatment. Furthermore, we found that endogenous IL-6 is partially involved in PGE2-stimulated osteoclast formation.
Amano
S
S
Department of Oral Microbiology, Meikai University School of Dentistry, Saitama, Japan.
Naganuma
K
K
Kawata
Y
Y
Kawakami
K
K
Kitano
S
S
Hanazawa
S
S
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D000818:Animals; D001862:Bone Resorption / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D012886:Skull; D013806:Theophylline / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D015650:24,25-Dihydroxyvitamin D 3; D013806:Theophylline; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone