Interleukin‐17 regulates the expressions of RANKL and OPG in human periodontal ligament cells via TRAF6/TBK1‐JNK/NF‐κB pathways

• Published in: Immunology 2015-03, Vol.144 (3), p.472-485
• Main Authors: Lin, Danping, Li, Lu, Sun, Ying, Wang, Weidong, Wang, Xiaoqian, Ye, Yu, Chen, Xu, Xu, Yan
• Format: Article
• Language: English
• Subjects: interleukin‐17; Original; osteoprotegerin; periodontal ligament cells; receptor activator for nuclear factor‐κB ligand; signal transduction
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12395

Summary Interleukin‐17 (IL‐17 or IL‐17A), a pleiotropic cytokine produced by T helper type 17 cells, is involved in the pathogenesis of various autoimmune and inflammatory disorders, including periodontitis. Although the ability of pro‐inflammation in periodontitis has been widely investigated, the other biological functions of IL‐17, including its role in bone remodelling and the underlying molecular mechanisms, 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, the two critical indicators for osteoclastogenesis, suggesting that IL‐17 may play a destructive role in the pathogenesis of periodontal bone remodelling. Pharmaceutical signal inhibitors targeted at mitogen‐activated protein kinases, Akt or nuclear factor‐κB signals, inhibited IL‐17‐induced RANKL and OPG regulation. Notably, the enhancement of RANKL was significantly blocked by the inhibitors of c‐Jun N‐terminal kinase and nuclear factor‐κB signals. The upstream signals were further investigated with the small interfering RNA. Both tumour necrosis factor receptor‐associated factor 6 and TNF receptor associated factor (TRAF) family member‐associated nuclear factor κ‐light‐chain enhancer of activated B cells (NF‐κB) activator (TANK)‐ binding kinase 1 were found to be the critical signal molecules for IL‐17‐dependent RANKL regulation in human periodontal ligament cells. These findings may provide comprehensive understanding of the role of IL‐17 in the pathogenesis of periodontitis and might also provide a reasonable route for periodontitis therapy.