Lyu Peiying, Liu Jianru, Ouyang Xiangying, Wang Yuanbo, Liu Wenyi, Zhong Jinsheng
Department of Periodontology, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
J Dent Sci. 2025 Jan;20(1):325-334. doi: 10.1016/j.jds.2024.07.008. Epub 2025 Jan 3.
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.
Experimental periodontitis models of wild-type and Nlrc5 knockout mice were established to detect alveolar bone loss. The inflammatory environment was established with lipopolysaccharide ( 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.
The Nlrc5 knockout mice exhibited greater alveolar bone loss in periodontitis. In the presence of 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.
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.
背景/目的：含核苷酸结合寡聚化结构域样受体家族凋亡相关斑点样蛋白（NLRC5）在天然免疫和适应性免疫中发挥调节作用。然而，其在牙周炎中的作用尚不清楚。本研究探讨NLRC5对牙周炎的影响及其潜在机制。
建立野生型和Nlrc5基因敲除小鼠的实验性牙周炎模型，检测牙槽骨吸收情况。用脂多糖（LPS）建立炎症环境。检测牙龈卟啉单胞菌LPS刺激后牙周膜干细胞（PDLSCs）中NLRC5的表达。在下调或上调NLRC5表达水平后，检测PDLSCs的炎性细胞因子水平和成骨能力。
Nlrc5基因敲除小鼠在牙周炎中表现出更严重的牙槽骨吸收。在LPS存在的情况下，NLRC5的表达降低。下调NLRC5可增加白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α（TNF-α）的表达。上调NLRC5可抑制核因子κB（NF-κB）信号通路，并抑制这些促炎因子的表达。NLRC5对PDLSCs的成骨分化具有正向调节作用。当NLRC5被敲低时，PDLSCs中的碱性磷酸酶（ALP）活性和矿化结节数量减少。相反，NLRC5的过表达增强了PDLSCs的成骨分化能力。NLRC5的过表达增加了炎症环境中PDLSCs的成骨分化。
NLRC5通过调节PDLSCs的功能影响牙周炎的进展。NLRC5通过抑制NF-κB降低炎症因子的表达，并对PDLSCs的成骨分化具有正向调节作用。
