Nicotine Attenuates Chondrocyte Inflammation via the α7nAChR-Mediated Inhibition of the HMGB1/TLR4/NF-κB Signaling Pathway.

Background: Chondrocyte inflammation is a major driver of osteoarthritis (OA). The cholinergic anti-inflammatory pathway (CAP) exhibits significant anti-inflammatory effects, with the α7 nicotinic acetylcholine receptor (α7nAChR) playing a pivotal role. However, it remains unclear whether α7nAChR alleviates chondrocyte inflammation through the regulation of the high mobility group box 1 (HMGB1)/TLR4/NF-κB signaling pathway. Methods: An in vitro model of chondrocyte inflammation was established by lipopolysaccharide (LPS) treatment of mouse cartilage cells. The protective effects of various concentrations of nicotine (Nic) on chondrocytes were assessed using the CCK-8 assay. To verify the critical role of α7nAChR, groups treated with methyllycaconitine (MLA, an α7nAChR antagonist) and siRNA-α7nAChR were included. Immunofluorescence was employed to observe the localization and expression of α7nAChR, HMGB1, and P65. Additionally, qRT-PCR, Western blot, and ELISA were employed to detect the expression of inflammation-related factors, cytokines, and MMPs. Results: The CCK-8 assay indicated that 1000 nmol/L Nic significantly restored chondrocyte proliferation activity reduced by LPS stimulation ( Conclusion: This study reveals that Nic alleviates chondrocyte inflammatory responses by activating α7nAChR and inhibiting the HMGB1/TLR4/NF-κB signaling pathway. These findings not only enhance the understanding of CAP's role in OA inflammation regulation but also provide a theoretical basis for exploring α7nAChR as a potential anti-inflammatory target. However, since the research is currently limited to in vitro cellular studies, further animal experiments are necessary to validate its clinical translational potential.