Journal
BONE
Volume 36, Issue 2, Pages 267-275Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2004.09.011
Keywords
IL-1 alpha; periodontal ligament; RANKL; ERK; PGE(2)
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Periodontitis, an inflammatory disorder of the supporting tissue of teeth, is one of the most common infectious diseases in humans. Peridontal pathogens promote inflammatory cytokines such as interleukin-1 (IL-1) and prostaglandin E-2 (PGE(2)), 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-1 alpha induced tartrate-resistant acid phosphatase positive (TRAP.) cell formation in a dose-dependent manner. IL-1 alpha up-regulated receptor activator of NF-kappa B 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-1 alpha stimulation inhibited IL-1 alpha-induced TRAP(+) cell formation. IL-1 alpha-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-1 alpha in PDL cells. IL-1 alpha activated ERK phosphorylation and PD98059 greatly inhibited both COX2 mRNA expression and PGE(2) production induced by IL-1 alpha in PDL cells. In contrast, NEMO binding domain (NBD) peptide, a specific inhibitor of NF-kappa B signaling, did not affect COX2, RANKL, or OPG mRNA expression induced by IL-1 alpha. These results suggest that IL-1 alpha. stimulates osteoclast formation by increasing the expression level of RANKL versus OPG via ERK-dependent PGE(2) production in PDL cells. (c) 2004 Elsevier Inc. All rights reserved.
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