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

Abstract

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.

Nicotine Regulates Autophagy of Human Periodontal Ligament Cells Through α7 nAchR That Promotes Secretion of Inflammatory Factors IL-1β and IL-8

“…α7 nAChR is a predominant subunit of nAChRs, as well as a potent target of the nicotine binding receptor [24]. In previous studies, we had con rmed the functional expression of α7 nAChR in PDL tissues and hPDLCs, and nicotine can up-regulate the expression of α7 nAChR [7,8,31]. Some existing studies had con rmed the complex connection between nAChRs, nicotine and autophagy in other cell types [17,29].…”

“…Previously, we had demonstrated the functional expression of α7 nAChR in periodontal ligament (PDL) tissues and human periodontal ligament cells (hPDLCs). Nicotine can enhance the expression of α7 nAChR in PDL tissues and hPDLCs, activate in ammation-related signaling pathways, and further regulate the secretion of in ammatory cytokines such as IL-1β and IL-8 [6][7][8].…”

Periodontal ligament stem cells in the periodontitis niche: inseparable interactions and mechanisms

“…97 A recent study has reported that PDLSCs could increase the ratio of the receptor activator of NF‐kB ligand/osteoprotegerin (RANKL/OPG) in response to orthodontic force to achieve bone reconstruction during tooth movement. 98 Consistently, the increased osteoclastic activity of P‐PDLSCs is found due to their increased expression of RANKL and decreased OPG level. 28 To be specific, increased RANKL can bind to the receptor activator of NF‐kB (RANK) expressed on osteoclast precursor cells to promote osteoclast differentiation and maturation, which may contribute to bone resorption.…”

“…However, as periodontal inflammation progresses, the oral mucosal barrier suffers from an impairment, followed by increased invasiveness of periodontal microflora and disorders of the host immune responses, which attenuate the function of resident PDLSCs 24,25 . Reciprocally, inflammatory functional alterations of PDLSCs may contribute to periodontal lesions, which aggravate periodontal inflammation and lead to continuous periodontal bone resorption 26–28 . In brief, the resident PDLSCs interact with the periodontitis niche, which are closely correlated to periodontal homeostasis.…”

The relationship between periodontal status and rheumatoid arthritis – systematic review

“…Tobacco smoking seems to induce changes ranging from decreased leukocyte chemotaxis to decreased production of immunoglobulins, but also to cause a stronger inflammatory reaction with increased release of potentially tissue-destructive substances such as reactive oxygen species, collagenase, serine proteases and proinflammatory cytokines. The current study indicates α7 nicotinic acetylcholine receptor (α7-nAChR) as able to mediate the potential synergistic effect of nicotine and inflammation [ 17 ].…”