IL-1- induced receptor activator of NF-kappa B ligand in human periodontal ligament cells involves ERK-dependent PGE2 production.
Periodontitis, an inflammatory disorder of the supporting tissue of teeth, is one of the most common infectious diseases in humans. Periodontal pathogens promote inflammatory cytokines such as interleukin-1 ( IL-1) and prostaglandin E2 (PGE2), resulting in alveolar bone destruction. In the present study, we examined the cellular and molecular mechanisms of IL-1-induced osteoclastogenesis using a coculture system of human periodontal ligament (PDL) cells and mouse spleen cells. IL-1alpha induced tartrate-resistant acid phosphatase positive (TRAP+) cell formation in a dose-dependent manner. IL-1alpha up-regulated receptor activator of NF-kappaB ligand ( RANKL) and down-regulated osteoprotegerin ( OPG) mRNA expression in PDL cells. The addition of cell-permeable PKI, an inhibitor of the cAMP/PKA signaling pathway, to the cocultures 8 h after the IL-1alpha stimulation inhibited IL-1alpha-induced TRAP+ cell formation. IL-1alpha-induced TRAP+ cell formation was completely blocked by either NS398, a selective inhibitor of cyclooxygenase (COX)-2, or PD98059, a specific inhibitor of extracellular signal-regulated kinase ( ERK). Pretreatment with NS398 and PD98059 also inhibited both the up-regulation of RANKL and the down-regulation of OPG expression by IL-1alpha in PDL cells. IL-1alpha activated ERK phosphorylation and PD98059 greatly inhibited both COX-2 mRNA expression and PGE(2) production induced by IL-1alpha in PDL cells. In contrast, NEMO binding domain (NBD) peptide, a specific inhibitor of NF-kappaB signaling, did not affect COX2, RANKL, or OPG mRNA expression induced by IL-1alpha. These results suggest that IL-1alpha stimulates osteoclast formation by increasing the expression level of RANKL versus OPG via ERK-dependent PGE2 production in PDL cells.[1]References
- IL-1-induced receptor activator of NF-kappa B ligand in human periodontal ligament cells involves ERK-dependent PGE2 production. Fukushima, H., Jimi, E., Okamoto, F., Motokawa, W., Okabe, K. Bone (2005) [Pubmed]
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