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

Osteoarthritis (OA), a multi-tissue joint disease, is examined in a new model using male CD1 mice. The study thoroughly analyses spontaneous OA in these mice to assess their suitability as a natural disease model. Knee joints from three to four and six to eight month old mice undergo histological examination, OARSI scoring, and immunohistochemistry to identify markers of cartilage development and bone formation. Quadriceps and gastrocnemius muscles are also evaluated for fibre cross-sectional area.

At 3-4 months, CD1 mice exhibit mild OA, which develops into moderate to severe disease by 6-8 months. The disease progresses across all joint compartments, characterized by cartilage loss, synovial hyperplasia, and fibrosis. Ligaments and the medial meniscus also display significant pathological remodeling, including proteoglycan-rich rounded cell regions and endochondral ossification with elevated COL2, SOX9, RUNX2, and ASPN expression.

While the gastrocnemius muscle demonstrates notable atrophy at 6-8 months, correlating with OA severity, quadriceps atrophy remains insignificant.

These results firmly position CD1 mice as a dependable spontaneous OA model that mirrors the complex multi-tissue nature of human disease. CD1 mice are globally accessible, affordable, genetically diverse, and frequently utilized, making them a practical and translationally relevant platform for studying the mechanisms of OA progression and testing therapies aimed at modifying disease throughout the entire joint.