Journal
IMMUNOLOGY
Volume 144, Issue 3, Pages 472-485Publisher
WILEY
DOI: 10.1111/imm.12395
Keywords
interleukin-17; osteoprotegerin; periodontal ligament cells; receptor activator for nuclear factor-kappa B ligand; signal transduction
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Funding
- National Natural Science Foundation of China [81170962, 81470749]
- Project of Science and Technology Department of Jiangsu Province [BK2011763]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [2014-37]
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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-kappa B 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-kappa B 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-kappa B 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 kappa-light-chain enhancer of activated B cells (NF-kappa B) 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.
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