Pathological musculoskeletal characterisation of a new model of spontaneous OA in CD1 mice

Osteoarthritis (OA) is a whole-joint disease involving pathological changes in cartilage, synovium, ligaments, menisci and periarticular muscle. This study provides a comprehensive musculoskeletal characterisation of spontaneous OA in male CD1 mice to evaluate their suitability as a model of naturally occurring disease. Knee joints from 3-4 and 6-8 month-old mice were analysed histologically, OARSI scoring and immunohistochemistry for markers of chondrogenesis and endochondral ossification. Quadriceps and gastrocnemius muscles were examined for fibre cross-sectional area.

CD1 mice displayed mild OA at 3-4 months, progressing to moderate-to-severe disease by 6– 8 months. Cartilage loss, synovial hyperplasia and fibrosis increased across compartments. Anterior cruciate and collateral ligaments, and medial meniscus exhibited marked pathological remodelling, including proteoglycan-rich rounded-cell regions and evidence of endochondral ossification with increased COL2, SOX9, RUNX2 and ASPN expression. Gastrocnemius muscle showed significant atrophy at 6-8 months, correlating with OA severity, whereas quadriceps atrophy was not significant.

These findings establish CD1 mice as a robust spontaneous OA model that recapitulates the multi-tissue complexity of human disease. Because CD1 mice are globally available, cost-effective, genetically diverse and frequently, this model offers a practical and translationally relevant platform for investigating whole-joint organ mechanisms of OA progression and for evaluating therapies aimed at modifying disease across the entire joint.