Inflammation has synergistic effect with nicotine in periodontitis by up-regulating the expression of α7 nAChR via phosphorylated GSK-3β.

Periodontitis is the leading cause of adult tooth loss, and those who smoke are at an increased risk of developing periodontitis. α7 nicotinic acetylcholine receptor (α7 nAChR) is proposed to mediate the potential synergistic effect of nicotine and inflammation in smoking-related periodontitis. However, this has not been experimentally demonstrated. We isolated and cultured human periodontal ligament stem cells (PDLSCs) from healthy and inflamed tissues. PDLSCs were treated with either inflammatory factors or nicotine. We measured expression of genes that are associated with osteogenic differentiation and osteoclast formation using RT-qPCR and Western blot analyses. Besides, immunohistochemical staining, micro-CT analysis and tartaric acid phosphatase staining were used to measure α7 nAChR expression and function. Inflammation up-regulated α7 nAChR expression in both periodontal ligament tissues and PDLSCs. The up-regulated α7 nAChR contributed to the synergistic effect of nicotine and inflammation, leading to a decreased capability of osteogenic differentiation and increased capability of osteoclast formation-induction of PDLSCs. Moreover, the inflammation-induced up-regulation of α7 nAChR was partially dependent on the level of phosphorylated GSK-3β. This study provides experimental evidence for the pathological development of smoking-related periodontitis and sheds new light on developing inflammation and α7 nAChR-targeted therapeutics to treat and prevent the disease.