Bmal1 knockout aggravates Porphyromonas gingivalis-induced periodontitis by activating the NF-κB pathway

Area of Science:

• Oral biology
• Chronobiology
• Immunology

Background:

• Circadian rhythm disorders and NF-κB signaling are implicated in periodontitis pathogenesis.
• The precise mechanisms linking circadian rhythm genes to periodontitis remain unclear.

Purpose of the Study:

• To investigate the impact of brain and muscle Arnt-like protein-1 (BMAL1) on the NF-κB pathway and inflammatory responses in periodontitis.
• To establish Bmal1 homozygous knockout and periodontitis mouse models for mechanistic studies.

Main Methods:

• Bone marrow-derived macrophages (BMDMs) from Bmal1 knockout mice were stimulated with lipopolysaccharides.
• Periodontitis severity was assessed via micro-CT and histological analysis.
• Gene and cytokine expression (Il-1b, Il-6, Tnfα, Nr1d1) and p65 nuclear translocation were quantified.

Main Results:

• Bmal1 knockout exacerbated periodontitis in mice, evidenced by increased bone resorption.
• BMAL1 deficiency activated the NF-κB pathway, indicated by increased p65 nuclear translocation in BMDMs.
• Inflammatory markers (Il-1b, Il-6, Tnfα) were upregulated, while Nr1d1 expression decreased in Bmal1-deficient BMDMs.

Conclusions:

• BMAL1 exhibits a protective effect against periodontitis.
• The circadian clock component BMAL1 influences periodontitis severity through modulation of the NF-κB pathway and inflammatory responses.