Objective: Biochemical and molecular changes involved in the pathophysiology of post-traumatic arthritis (PTOA) have not been fully understood. This study used non-invasive mouse models to study biochemical, biomechanical and pain-related behavior changes induced in mice following repetitive mechanical knee loading. Mouse models were used to reflect the effects of the early stages of PTOA in humans. Methods: Forty-eight twelve week old male mice were obtained for three groups: normal control

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... hout mechanical loading, trauma (24 hours after loading), and PTOA (early OA) groups. For the non-invasive PTOA mouse model, cyclic comprehensive loading (9 N) was applied on the left knee joint of each mouse. Biochemical and molecular changes induced by mechanical loading were analyzed after loading was completed. Blood and cartilage were collected and further examined using gene expression analysis. Grading of the tissue sections was completed using the osteoarthritis research society international (OARSI) scale. Biomechanical features of mechanically loaded knee joints were determined after 24 hours (Trauma) and three weeks (PTOA) post-mechanical loading sessions to examine the development of PTOA, respectively. Results: The loaded left knee joint showed a greater ROS/RNS signal than the right knee that was not loaded. There was an increase in cartilage damage and MMP activity in the affected knee as the intensity of MabCII680 and MMP750 signal increased in the mechanical loaded joints as compared to unloaded control knee joints. There was also an increase in the difference of viscoelastic energy dissipation ability (tan δ) in PTOA. The OA score increased significantly in mechanically loaded knee joints. Conclusion: This study showed that biomechanical, biochemical, and behavioral characteristics of the murine PTOA groups are significantly different from the control group. These results validate that the current mouse model can be used for translational studies to examine PTOA.