Fig. 4: Intra-articular injection of lentiviruses expressing FOXO3 attenuates OA lesions caused by a HFD in mice.

a, b SO&FG staining (a) as well as H&E staining (b) was performed to depict the cartilage area of joints in mice fed with a high-fat diet after intra-articular injection of lentiviruses expressing FOXO3. Black boxes and dashed lines indicate representative areas of joint cartilage, which were further magnified for detailed examination. n = 6 mice per group. c The extent of cartilage damage was assessed using the OARSI scoring system based on the staining in (a). d, e Micro-CT (e) was conducted to assess the osteophyte volume (top) in joints from mice fed with a high-fat diet after intra-articular injection of lentiviruses expressing FOXO3. Osteophyte scores were quantified (d). n = 6 mice per group. f, g Quantitative micro-CT analysis was performed on the tibial subchondral bone (e), measuring trabecular bone volume per total volume (BV/TV) (f) and trabecular thickness (Tb.Th) (g) in joints from mice fed with an HFD after intra-articular injection of lentiviruses expressing FOXO3. h–k, IHC staining of Col2a1 (h) and Mmp13 (j) was performed on the articular cartilage of joints from mice fed with an HFD after intra-articular injection of lentiviruses expressing FOXO3. The percentage of positive cells in the cartilage was quantified. n = 6 mice per group. l, m TRAP staining on the tibial subchondral bone in mice fed with an HFD after intra-articular injection of lentiviruses expressing FOXO3. The percentage of positive cells in the subchondral bone of the cartilage was quantified. n = 6 mice per group. n–s IF staining of TRAP (red) (n), γH2AX (red) (p), and Perilipin-1 (red) (r) was performed on the subchondral bone of joints from mice fed with an HFD after intra-articular injection of lentiviruses expressing FOXO3. The percentage of positive cells in the subchondral bone of the cartilage was quantified. n = 6 mice per group. The sham group received an injection of a lentiviral blank vector, while the FOXO3 group received an injection of a lentivirus expressing FOXO3. Data are represented as mean ± s.d. One-way ANOVA was performed. All exact p-values have been indicated in the figures. Source data are provided as a Source Data file.