Fig. 7. Intra-articular T3-EV injection reversed OA progression by regulating the miR-455/SOX11/FOXO signaling axis.

A To determine whether T3-EV transplantation could reduce or reverse the progression of OA, intra-articular injection of T3-EV labeled with Dir was performed for rats with DMM surgery. B PKH26-labeled EVs (red) to detect their internalization by BMSC in vitro. C Intra-articular delivery of the Dir-label T3-EVs (left: red) were monitored with in vivo fluorescence imaging to evaluate the near-infrared imaging effect and distribution of EVs for 12 weeks, showing an ideal intra-articular delivery effect (right). D–F Histological assessments of joint cartilage with D HE (left column), TB staining (right column), and E, F immunostaining for ACAN, MMP13, miR-455, SOX11, and FOXO1 in different groups. G–J Quantification and comparison of histological grade for OA progression in different groups (n = 8 for each). Joint destruction severity was determined with OARSI score, osteophyte formation, subchondral bone plate thickness, and synovial inflammation as previously reported^60–62. Saline: OA model group with saline injection; un-EV: only untreated EVs were injected for OA treatment; T3-EV: TGFβ3-treated EVs were injected for OA treatment. *P < 0.05, **P < 0.01, ***P < 0.001, NS not significant. #p < 0.05 compared to the un-EV gel group.