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.