Convergent Activation of NF-κB and STAT3 Drives Cartilage Degeneration in a Murine Model of BCG-Induced Arthritis

Reactive arthritis induced by Mycobacterium tuberculosis (M.tb) causes severe cartilage degradation, yet the underlying mechanisms remain elusive. This study investigated the molecular mechanisms and potential therapeutic targets for M.tb-induced cartilage damage. A mouse model of BCG-induced tuberculous arthritis was established. Cartilage matrix degradation, chondrocyte apoptosis, and metabolic balance were evaluated histologically and biochemically. Activation of the NF-κB p65 and STAT3 signaling pathways was assessed, followed by pharmacological inhibition. BCG infection significantly reduced cartilage matrix content and promoted chondrocyte apoptosis, disrupting the metabolic balance between matrix synthesis and degradation. Mechanistically, BCG markedly activated the NF-κB p65 and STAT3 pathways in articular cartilage. Pharmacological inhibition of these pathways effectively prevented cartilage matrix loss and reduced chondrocyte apoptosis at the protein level. BCG induces cartilage damage through activation of NF-κB p65 and STAT3 pathways, leading to chondrocyte apoptosis and matrix catabolism. Targeting these signaling cascades represents a promising therapeutic strategy for preventing cartilage degeneration in tuberculous arthritis.