Systemic Lupus Erythematosus Exacerbates Hip Arthritis by Promoting Chondrocyte Pyroptosis in the Femoral Head via...

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by chronic inflammation and immune dysregulation, significantly impacting multiple organ systems, including the joints. While SLE is known to contribute to musculoskeletal complications, its role in hip arthritis development and the underlying mechanisms remain poorly understood. This study aims to investigate the relationship between SLE and hip arthritis progression using MRL/lpr mice, which exhibit early-onset SLE, compared with MRL/MpJ control mice at 14 weeks of age. Through comprehensive histological, immunohistochemical and molecular analyses, we evaluated articular cartilage (AC) degeneration, extracellular matrix (ECM) metabolism, inflammatory responses, and chondrocyte pyroptosis. Our results demonstrated that MRL/lpr mice developed an accelerated hip arthritis-like phenotype, manifesting as enhanced AC degeneration, impaired chondrocyte proliferation, heightened apoptosis and promoted inflammatory cytokine production. Notably, SLE markedly stimulated chondrocyte pyroptosis by increasing pyroptosis-related proteins, including NLRP3, ASC, CASPASE-1 and GSDMD, via activating the NF-κB pathway. These findings establish a novel mechanistic link between SLE and hip arthritis progression, demonstrating that SLE promotes chondrocyte pyroptosis to exacerbate AC degeneration via NF-κB activation, highlighting chondrocyte pyroptosis as a key driver of SLE-associated hip arthritis and a potential therapeutic target for mitigating SLE-induced joint manifestations.