Circadian rhythm disruption exacerbates the progression of macrophage dysfunction and alveolar bone loss in periodontitis

• Published in: International immunopharmacology 2023-03, Vol.116, p.109796-109796, Article 109796
• Main Authors: Ma, Xueying, Chen, Xin, Duan, Zhonghua, Wu, Yuqiong, Shu, Jiaen, Wu, Pei, Zhao, Yiguo, Wang, Xu, Wang, Yuhua
• Format: Article
• Language: English
• Subjects: Alveolar bone loss; Alveolar Bone Loss - metabolism; Animals; Circadian rhythm disruption; Histone Demethylases - metabolism; Inflammation - metabolism; Kdm6a; Macrophage; Macrophages; Mice; Periodontitis; Periodontitis - metabolism; Porphyromonas gingivalis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.109796

•Circadian rhythm disruption promoted the development of periodontitis by promoting the proinflammatory response.•Kdm6a deficiency in macrophages alleviated periodontitis.•The aggravation of periodontitis by CRD can be attenuated by Kdm6a deletion in macrophages. Macrophages are highly implicated in the progression of periodontitis, while circadian rhythm disruption (CRD) promotes the inflammatory response of macrophages in many diseases. However, the effects of CRD on periodontitis and the role of macrophages in this process remain unclear. Histone lysinedemethylase6a (Kdm6a), a histone demethylase, has recently been identified as a key regulator of macrophage-induced inflammation. Here, we established an experimental periodontitis model by injecting lipopolysaccharide (LPS) derived from Porphyromonas gingivalis with or without periodontal ligation in mice exposed to an 8-h time shift jet-lag schedule every 3 days. By histomorphometry, tartrate acid phosphatase (TRAP) staining, RT-qPCR, ELISA, immunohistochemistry and immunofluorescence analysis, we found that CRD promoted the inflammatory response, alveolar bone resorption, macrophage infiltration and Kdm6a expression in macrophages. Macrophage-specific Kdm6a knockout mice were further used to elucidate the effects of Kdm6a deficiency on periodontitis. Kdm6a deletion in macrophages rescued periodontal tissue inflammation, osteoclastogenesis, and alveolar bone loss in a mouse model of periodontitis. These findings suggest that CRD may intensify periodontitis by increasing the infiltration and activation of macrophages. Kdm6a promotes the inflammatory response in macrophages, which may participate in aggravated periodontitis via CRD.