Sophoridine attenuates osteoarthritis progression: association with suppression of chondrocyte pyroptosis via inhibiting NF-κB signaling pathway.

INTRODUCTION

Osteoarthritis (OA) is a degenerative musculoskeletal disease characterized by cartilage degradation and inflammation. Sophoridine (SR), a quinolizidine alkaloid from traditional Chinese herbs, has demonstrated anti-inflammatory properties, but its role in OA is unknown.

METHODS

The effects of SR on chondrocyte viability were assessed using the Cell Counting Kit-8 (CCK-8) assay. Interleukin-1β (IL-1β)-stimulated murine primary chondrocytes were used as an in vitro OA model. Extracellular matrix (ECM) synthesis was evaluated by toluidine blue staining. Key molecules involved in ECM metabolism, inflammation, and pyroptosis, as well as nuclear factor kappa B (NF-κB) signaling activity, were analyzed using quantitative reverse transcription PCR (RT-qPCR), Western blotting, and immunofluorescence. Chondrocyte morphological changes were examined by scanning electron microscopy. To validate causal mechanisms, a functional rescue experiment was performed in vitro using a specific NF-κB activator. For in vivo studies, an anterior cruciate ligament transection (ACLT)-induced murine OA model was established to evaluate the therapeutic efficacy of SR. OA progression was assessed by functional tests, micro-computed tomography (micro-CT), and histopathological analyses. Immunohistochemistry and immunofluorescence were further performed to evaluate molecular and signaling alterations in cartilage tissues.

RESULTS

In IL-1β-stimulated chondrocytes, SR (20 and 40 μg/mL) significantly inhibited ECM degradation and suppressed the expression of pro-inflammatory cytokines. In vivo studies utilizing a well-established murine OA model induced by ACLT demonstrated that intraperitoneal SR administration (7.5 and 15 mg/kg/day for 8 weeks) markedly ameliorated cartilage destruction and inflammation. Notably, SR prominently reduced chondrocyte pyroptosis and suppressed NF-κB pathway activation. Mechanistically, co-treatment with an NF-κB activator significantly reversed the SR-mediated protection of ECM components and abolished the downregulation of key pyroptosis-related proteins.

CONCLUSION

Our study indicates that SR effectively attenuates OA progression, which was associated with the suppression of chondrocyte pyroptosis and inflammation via NF-κB signaling pathway inhibition, suggesting SR as a promising therapeutic agent for OA treatment.