title: IL-17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1-JNK/NF-κB pathways.
abstract: Interleukin-17 (IL-17 or IL-17A), a pleiotropic cytokine produced by T helper (Th) 17 cells, is involved in the pathogenesis of various autoimmune and inflammatory disorders, including periodontitis. Although the ability of pro-inflammation in periodontitis have been widely investigated, the other biological functions of IL-17, including its role in bone remodeling and the underlying molecular mechanism, have not been well clarified. In the present study, IL-17 could significantly enhance the expression of receptor activator for nuclear factor-κB ligand (RANKL) and inhibit the expression of osteoprotegerin (OPG) in human periodontal ligament cells (hPDLCs), the two critical indicators for osteoclastogenesis, suggesting IL-17 may play a destructive role in the pathogenesis of periodontal bone remodeling. Pharmaceutical signal inhibitors targeted at MAPKs, Akt or NF-κB signals, inhibited IL-17-induced RANKL and OPG regulation. Notably, the enhancement of RANKL was significantly blocked by the inhibitors of JNK and NF-κB signals. The upstream signals were further investigated with the small interfering RNA (siRNA). Both TRAF6 and TBK1 were found to be the critically signal molecules for IL-17-dependent RANKL regulation in hPDLCs. These findings may provide comprehensive understanding of the role of IL-17 in the pathogenesis of periodontitis and might also provide a reasonable way for periodontitis therapy. This article is protected by copyright. All rights reserved.
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Danping
authors.initials: D
authors.lastname: Lin
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Ye
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
keywords: Interleukin-17; Osteoprotegerin; RANK Ligand; periodontal ligament cells; signal transduction