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Updated: Sep 7, 2025
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
NLRC5 modulates bone metabolism and plays a role in periodontitis
Weiping Wang1, Wenyi Liu1, Jianru Liu1
1Department of Periodontology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Introduction:
NOD-like receptor C5 (NLRC5) plays a significant role in the immune system, and is one of the largest members of the pattern recognition receptor family. Previous studies have found that NLRC5 might be involved in the regulation of various diseases, such as fibrotic diseases and cancers; however, its effect on bone metabolism-related diseases has not been reported.
Methods:
Skeletons of Nlrc5-/- mice generated by CRISPR/Cas9 and wild-type (WT) mice were compared using X-ray, micro-computed tomography, double labeling, and histological examination. Tartrate-resistant acid phosphatase and pit-absorption assays were performed to evaluate the effect of NLRC5 on osteoclasts differentiation and osteoclastic capacity. The influence of NLRC5 on osteoblasts differentiation and bone formation were studied using alkaline phosphatase and alizarin red staining, respectively. Experimental periodontitis was induced by Porphyromonas gingivalis infection and ligature to investigate the role of NLRC5 in inflammatory periodontal bone loss.
Results:
Adenovirus-mediated NLRC5 overexpression in human bone marrow mesenchymal stem cells regulated osteogenesis positively. The femoral osteogenesis ability was significantly weakened in Nlrc5-/- mice. Histology showed that the area of the femoral trabeculae in the Nlrc5-/- mice was less than that in the WT mice, and radiology suggested that the Nlrc5-/- mice had fewer trabeculae and a thinner bone cortex than those of the WT mice. Nlrc5 knockout decreased osteoblast mineralization and increased osteoclastogenesis in vitro. NLRC5 was downregulated in periodontitis and P. gingivalis infection. In the experimental periodontitis model, the alveolar bone loss, inflammatory cell infiltration, and inflammatory cytokines secretion (interleukin [IL]-1β, IL-6, and tumor necrosis factor alpha [TNF-α]) in the Nlrc5-/- mice were significantly enhanced compared to WT mice.
Conclusion:
We verified a novel role of NLRC5 in bone metabolism by regulating both osteoclasts activity and osteoblasts activity. Our results revealed a protective effect of NLRC5 against periodontal inflammation and alveolar bone destruction. NLRC5 could be a novel treatment target to prevent periodontal bone destruction.
Insights
NOD-like receptor C5 (NLRC5) regulates bone metabolism by influencing osteoblasts and osteoclasts. Loss of NLRC5 exacerbates periodontal bone loss and inflammation, suggesting it as a therapeutic target.
Area of Science:
- Immunology
- Bone Biology
- Periodontal Disease
Background:
- NOD-like receptor C5 (NLRC5) is a key pattern recognition receptor involved in immune responses.
- Previous research linked NLRC5 to fibrotic diseases and cancers, but its role in bone metabolism was unknown.
Purpose of the Study:
- To investigate the role of NLRC5 in bone metabolism and periodontal bone loss.
- To determine NLRC5's effect on osteoblasts and osteoclasts.
- To assess NLRC5's function in an experimental periodontitis model.
Main Methods:
- Comparative analysis of Nlrc5 knockout (Nlrc5-/-) and wild-type (WT) mice using skeletal imaging and histology.
- In vitro assays to assess osteoblast and osteoclast differentiation and activity.
- Induction of experimental periodontitis in mice to evaluate alveolar bone loss and inflammatory responses.
Main Results:
- NLRC5 overexpression promoted osteogenesis in human mesenchymal stem cells.
- Nlrc5-/- mice exhibited impaired femoral osteogenesis, reduced trabecular bone, and thinner cortical bone.
- NLRC5 deficiency increased osteoclastogenesis and decreased osteoblast mineralization in vitro.
- NLRC5 was downregulated in periodontitis models; Nlrc5-/- mice showed enhanced alveolar bone loss, inflammation, and pro-inflammatory cytokine secretion.
Conclusions:
- NLRC5 plays a novel role in bone metabolism by modulating both osteoclast and osteoblast activity.
- NLRC5 demonstrates a protective effect against periodontal inflammation and alveolar bone destruction.
- NLRC5 represents a potential therapeutic target for preventing periodontal bone loss.
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