title: Nicotine favors osteoclastogenesis in human periodontal ligament cells co-cultured with CD4(+) T cells by upregulating IL-1β.
abstract: Periodontitis, which is the main cause of tooth loss, is one of the most common chronic oral diseases in adults. Tooth loss is mainly a result of alveolar bone resorption, which reflects an increased osteoclast formation and activation. Osteoclast formation in periodontal tissue is a multistep process driven by osteoclastogenesis supporting cells such as human periodontal ligament (PDL) cells and CD4(+) T cells. Inflammatory cytokines, such as interleukin-1β (IL-1β), can induce osteoclastogenesis by affecting the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in human PDL cells. Nicotine, the major component in tobacco smoking and a specific agonist of the α7 nicotinic acetylcholine receptor (α7 nAChR), has been proven to regulate the expression of inflammatory cytokines in smoking-associated periodontitis. In this study, we investigated the mechanism(s) through which nicotine affects osteoclastogenesis in human PDL cells co-cultured/non-co-cultured with CD4(+) T cells. Human PDL cells were stimulated with nicotine (10-5 M) and/or α-bungarotoxin (α-BTX, specific antagonist of α7 nAChR, 10-8 M) before being co-cultured with CD4(+) T cells. Compared with mono-culture systems, stimulation with nicotine caused an increased secretion of IL-1β in serum of human PDL cell-CD4(+) T cell co-culture, and the expression of RANKL in human PDL cells was further upregulated co-cultured with CD4(+) T cells, while no differences were observed in the expression of OPG between the co-culture and mono-culture systems. Our data suggested that nicotine upregulated IL-1β secretion, further upregulated RANKL expression in smoking-associated periodontitis, which may aid in the better understanding of the relationship between nicotine and alveolar bone resorption.
authors: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors: Li-Zheng
authors: LZ
authors: Wu
authors: Duo-Mo
authors: DM
authors: Duan
authors: Ying-Feng
authors: YF
authors: Liu
authors: Xin
authors: X
authors: Ge
authors: Zhi-Fei
authors: ZF
authors: Zhou
authors: Xiao-Jing
authors: XJ
authors: Wang
mesh_terms: D000704:Analysis of Variance; D002038:Bungarotoxins; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D053245:RANK Ligand / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002038:Bungarotoxins; D053583:Interleukin-1beta; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D009538:Nicotine