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Isolation, Processing and Analysis of Murine Gingival Cells
Published on: July 2, 2013
Circadian rhythm disruption exacerbates the progression of macrophage dysfunction and alveolar bone loss in
Xueying Ma1, Xin Chen2, Zhonghua Duan1
1Department of Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai 200011, China.
Abstract:
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.
Insights
Circadian rhythm disruption exacerbates periodontitis by increasing macrophage activity. Histone lysinedemethylase6a (Kdm6a) in macrophages drives this inflammation, and its removal protects against bone loss.
Area of Science:
- Oral biology
- Immunology
- Chronobiology
Background:
- Macrophages play a key role in periodontitis progression.
- Circadian rhythm disruption (CRD) is known to promote macrophage inflammation in various diseases.
- The specific impact of CRD on periodontitis and the role of macrophages remain unclear.
Purpose of the Study:
- To investigate the effects of CRD on periodontitis.
- To elucidate the role of macrophages and histone lysinedemethylase6a (Kdm6a) in CRD-exacerbated periodontitis.
Main Methods:
- An experimental periodontitis model was created in mice subjected to a jet-lag schedule.
- Techniques included histomorphometry, TRAP staining, RT-qPCR, ELISA, immunohistochemistry, and immunofluorescence.
- Macrophage-specific Kdm6a knockout mice were utilized.
Main Results:
- CRD significantly promoted inflammation, alveolar bone resorption, and macrophage infiltration in periodontitis models.
- Kdm6a expression was upregulated in macrophages under CRD conditions.
- Deletion of Kdm6a in macrophages ameliorated periodontal inflammation and bone loss.
Conclusions:
- CRD intensifies periodontitis by enhancing macrophage infiltration and activation.
- Kdm6a in macrophages is a critical mediator of CRD-induced inflammation and periodontitis progression.
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