Mitogen-activated protein kinases mediate interleukin-1β-induced receptor activator of nuclear factor-κB ligand expression in human periodontal ligament cells

• Published in: Journal of periodontal research Vol. 42; no. 4; pp. 367 - 376
• Main Authors: Oikawa, A., Kobayashi, M., Okamatsu, Y., Shinki, T., Kamijo, R., Yamamoto, M., Hasegawa, K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2007; Blackwell
• Subjects: Biological and medical sciences; human periodontal ligament cells; interleukin-1β; Medical sciences; mitogen-activated protein kinases; Otorhinolaryngology. Stomatology; receptor activator of nuclear factor-κB ligand; Human; human periodontal ligament cells; Nuclear receptor; interleukin-1 p; Enzyme; Ligand; Stomatology; Mitogen-activated protein kinase; Interleukin 1β; Periodontal ligament; mitogen-activated protein kinases; Interleukin 1; receptor activator of nuclear factor-KB ligand; Transcription factor NFκB; Cell
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/j.1600-0765.2006.00959.x

Background and Objective:  Interleukin‐1β‐stimulated receptor activator of nuclear factor‐κB ligand (RANKL) expression in human periodontal ligament cells is partially mediated by endogenous prostaglandin E2, whereas mitogen‐activated protein kinases (MAPKs) are implicated in regulating various interleukin‐1‐responsive genes. We investigated herein the involvement of MAPKs in interleukin‐1β‐stimulated RANKL expression in human periodontal ligament cells. Material and Methods:  Human periodontal ligament cells were pretreated separately with specific inhibitors of MAPKs, including extracellular signal‐regulated kinase, p38 MAPK and c‐Jun N‐terminal kinase, and subsequently treated with interleukin‐1β. Following each treatment, the phosphorylation of each MAPK, the expression of RANKL, and the production of prostaglandin E2 were determined. RANKL activity was evaluated using an assay to determine the survival of prefusion osteoclasts. Results:  Interleukin‐1β induced RANKL expression at the mRNA and protein levels, as well as RANKL activity in human periodontal ligament cells. Interleukin‐1β also activated extracellular signal‐regulated kinase, p38 MAPK, and c‐Jun N‐terminal kinase. Pretreatment with each MAPK inhibitor partially, but significantly, suppressed interleukin‐1β‐induced RANKL expression and its activity, as well as prostaglandin E2 production. Conclusion:  In human periodontal ligament cells, three types of MAPK inhibitor may abrogate RANKL expression and activity induced by interleukin‐1β, directly or indirectly through partial suppression of prostaglandin E2 synthesis. In addition, extracellular signal‐regulated kinase, p38 MAPK, and c‐Jun N‐terminal kinase signals may co‐operatively mediate interleukin‐1β‐stimulated RANKL expression and its activity in those cells.