NLRX1 alleviates lipopolysaccharide-induced apoptosis and inflammation in chondrocytes by suppressing the activation of NF-κB signaling.

Osteoarthritis (OA) is a chronic debilitating disease characterized by joint degeneration. Excessive chondrocyte apoptosis and inflammation contributes to articular cartilage destruction in OA pathology. Nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) has emerged as a critical regulator of inflammation that participates in the pathology of diverse diseases. To date, little is known about the role of NLRX1 in OA. In the present study, we aimed to explore the function of NLRX1 in lipopolysaccharide (LPS)-induced injury in chondrocytes, an in vitro model of OA. NLRX1 mRNA was detected by quantitative polymerase chain reaction (qPCR) analysis. Protein expression of NLRX1, phosphorylated IκB kinase β (IKKβ), and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by western blot. Cell viability was assessed by the MTT assay. Cell apoptosis was evaluated by measuring caspase-3 activity. Cytokine release was assessed by enzyme-linked immunosorbent assay (ELISA). NF-κB signaling activation was analyzed with a luciferase reporter assay. Herein, our results revealed that NLRX1 expression was markedly decreased in LPS-treated chondrocytes. Functional experiments demonstrated that NLRX1 overexpression significantly improved cell viability and attenuated LPS-treated chondrocyte apoptosis and inflammation, while NLRX1 silencing caused the opposite effects. Moreover, our results showed that NLRX1 regulated LPS-induced NF-κB signaling activation. Notably, NF-κB signaling inhibition significantly reversed the NLRX1-knockdown-mediated enhanced effects on LPS-induced apoptosis and inflammation. Overall, these results demonstrate that NLRX1 alleviates LPS-induced apoptosis and inflammation in chondrocytes by negatively regulating NF-κB signaling, results that indicate an anti-inflammatory role for NLRX1 in OA. Our findings suggest that NLRX1 may serve as a potential therapeutic target for OA.