Propionate attenuates osteoarthritis progression by regulating the gut-joint axis

Osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage degradation, inflammation, and pain. Growing evidence indicates that dysregulation of the gut-joint axis contributes to OA progression. This study investigated the therapeutic potential of propionate, a gut-derived short-chain fatty acid, in OA.

A monosodium iodoacetate (MIA)-induced OA rat model was used to evaluate the effects of propionate on pain and inflammation through behavioral assessments, histological analysis, and gut microbiota profiling. The intestinal environment was further assessed by histology, tight junction protein analysis, and microbiota characterization. Human OA chondrocytes were analyzed using qPCR and RNA sequencing following IL-1β stimulation with or without propionate treatment.

Propionate attenuated OA severity in MIA-induced rats by improving pain behaviors, preserving cartilage structure, reducing nociceptive and inflammatory markers, and restoring intestinal barrier function and microbial balance. In human OA chondrocytes, propionate modulated inflammatory and ECM-related gene expression, promoted autophagy, and suppressed catabolic and inflammatory cell death pathways, highlighting its therapeutic potential in OA.

Propionate, a gut-derived SCFA, alleviated pain, protected cartilage, reduced inflammation, restored gut barrier integrity, and rebalanced microbiota in OA rats. In human OA chondrocytes, it upregulated ECM-related genes, downregulated inflammatory mediators, and enhanced autophagy. These findings suggest that propionate may serve as a promising disease-modifying therapy for OA.