Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 affects the progression of periodontitis by regulating the function of periodontal membrane cells

Abstract

Background/purpose

Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 (NLRC5) plays a regulatory role in innate and adaptive immunity. However, its role in periodontitis remains unclear. This study investigated the effects of NLRC5 on periodontitis and the underlying mechanism.

Materials and methods

Experimental periodontitis models of wild-type and Nlrc5 knockout mice were established to detect alveolar bone loss. The inflammatory environment was established with Porphyromonas. gingivalis lipopolysaccharide (P. gingivalis LPS). The expression of NLRC5 in periodontal ligament stem cells (PDLSCs) were detected with P. gingivalis LPS stimulated. After knocking-down or overexpressing the NLRC5 expression level, the inflammatory cytokine level and osteogenic ability of PDLSCs were detected.

Results

The Nlrc5 knockout mice exhibited greater alveolar bone loss in periodontitis. In the presence of P. gingivalis LPS, the expression of NLRC5 decreased. Downregulating NLRC5 increased the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). Upregulated NLRC5 inhibited nuclear factor kappa-B (NF-κB) signaling and inhibited the expression of those proinflammatory factors. NLRC5 had a positive regulatory effect on the osteogenic differentiation of PDLSCs. When NLRC5 was knocked down, the ALP activity and the number of mineralized nodules in PDLSCs decreased. Conversely, overexpression of NLRC5 enhanced the osteogenic differentiation ability of PDLSCs. Overexpression of NLRC5 increased the osteogenic differentiation of PDLSCs in inflammatory environments.

Conclusion

NLRC5 affects the progression of periodontitis by regulating the function of PDLSCs. NLRC5 reduced the expression of inflammatory factors by inhibiting NF-κB, and had a positive regulatory effect on the osteogenic differentiation of PDLSCs.