IL-1-induced receptor activator of NF-κB ligand in human periodontal ligament cells involves ERK-dependent PGE2 production

Hidefumi Fukushima, Eijiro Jimi, Fujio Okamoto, Wataru Motokawa, Koji Okabe

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

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-1α induced tartrate-resistant acid phosphatase positive (TRAP+) cell formation in a dose-dependent manner. IL-1α up-regulated receptor activator of NF-κB 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-1α stimulation inhibited IL-1α-induced TRAP+ cell formation. IL-1α-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-1α in PDL cells. IL-1α activated ERK phosphorylation and PD98059 greatly inhibited both COX-2 mRNA expression and PGE2 production induced by IL-1α in PDL cells. In contrast, NEMO binding domain (NBD) peptide, a specific inhibitor of NF-κB signaling, did not affect COX2, RANKL, or OPG mRNA expression induced by IL-1α. These results suggest that IL-1α stimulates osteoclast formation by increasing the expression level of RANKL versus OPG via ERK-dependent PGE2 production in PDL cells.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalBone
Volume36
Issue number2
DOIs
Publication statusPublished - Feb 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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