Abstract
OBJECTIVE: While physiological loads maintain cartilage health, both joint overload and abnormal joint mechanical loading contribute to osteoarthritis (OA) development. Here, we examined the role of abnormal mechanical loading on joint health by comparing the severity of OA development following a single overload event and repetitive joint overloads. METHOD: Cyclic tibial compression was applied to the left limbs of 26-week-old male mice at a peak load of 9N for either a single bout or daily bouts to initiate OA disease. Joint damage severity was morphologically examined using histology and microcomputed tomography at 6 weeks following the start of loading. Early-stage transcriptomic responses to loading were evaluated. RESULTS: Joint damage was more severe at 6 weeks following a single bout of loading than after daily loading bouts. Severe cartilage damage, subchondral plate erosions, and soft tissue calcifications occurred following the single bout of loading. Daily loading bouts resulted in less severe cartilage damage and preserved subchondral plate integrity. A diverging transcriptomic response was identified in cartilage at 1 week with increased expression of fibrosis- and inflammation-related genes following a single bout of loading compared to daily loading. CONCLUSIONS: Even applied at hyperphysiological load magnitudes known to initiate cartilage damage, repetitive loading may induce protective effects in the joint and attenuate OA progression over time relative to a single bout of loading. Our findings suggest the potential of mechanotherapies that use repetitive loading as disease-modifying treatments for OA disease.