Collagenase-induced OA mice model

Male C57BL/6 mice (12 weeks old, SPF, Second Affiliated Hospital of HMU Animal Centre, Harbin, China) were obtained to establish the collagenase-induced OA model with some modifications (Van Der Kraan et al., 1990). Treatment of collagenase type VII could result in knee joint instability by damaging the cruciate plus collateral ligaments. Finally, chronic synovial activation as well as cartilage destruction were induced, representing an OA-like phenotype. Briefly, 5 U collagenase type VII (Sigma-Aldrich) was injected intraarticularly into the right knee on days 0 and 2. The mice were then grouped as follows (n = 6 for each group): OA control, SMSCs-sEV, Vector-SMSCs-sEV, OE-circPARD3B-SMSCs-sEV (mice with OA treated with sEV [100 µg] in PBS [10 µl], twice a week) and a normal control group (NC) (without collagenase injection). Intraarticular injection in mice with OA were administered from day 7 to day 42. The NC group and the OA control group were administered with equal volume of PBS through injection.