Extended Data Fig. 7: The inhibition of Ferroptosis partially ameliorates the muscle mass and function of Quadriceps in OA joints.
(a) Experimental design for targeted delivery of anti-ferroptosis genes into Quadriceps using adeno-associated virus (AAV). (B-F) The assessment of AAV delivery efficiency was performed at 3 weeks post-AAV-mediated gene therapy using (b) an in vivo imaging system and (c–f) western blotting analysis and quantitative results at D12 (n = 3). (g) Data of RH-Dual Stance in mice with or without AAV treatment at S12 and D12. (n = 12 Sham-AAVControl-G, n = 13 Sham-AAVMHCK7-GPX4, n = 12 Sham-AAVControl-F, n = 11 Sham-AAVMHCK7-FSP1, n = 13 DMM-AAVControl-G, n = 15 DMM-AAVMHCK7-GPX4, n = 13 DMM-AAVControl-F, n = 15 DMM-AAVMHCK7-FSP1). (h) Quantification of lipid peroxidation (LPO) levels in the Quadriceps of mice with or without AAV treatment at S12 and D12. (n = 5 Sham, n = 5 DMM-AAVControl-G, n = 4 DMM-AAVMHCK7-GPX4, n = 5 DMM-AAVControl-F, n = 6 DMM-AAVMHCK7-FSP1). (i-l) The distribution and mean CSA of the total, MyHC-IIa, and MyHC-IIb myofibers in the Quadriceps of mice with or without AAV treatment at S12 and D12 (n = 5 Sham-AAVControl-G, n = 6 Sham-AAVControl-G, n = 5 DMM-AAVControl-G, n = 6 DMM-AAVMHCK7-GPX4; n = 5 Sham, n = 5 DMM-AAVControl-F, n = 6 DMM-AAVMHCK7-FSP1). Data are presented as mean±s.e.m. unless otherwise noted, all statistical tests were two-sided unless otherwise noted, and n represented biological replicates unless otherwise noted. One-way ANOVA with Bonferroni test (g, h (FSP1 over-expression), j (Total), j (IIa), j (Ratio of IIa to IIb), l). One-way ANOVA with Tamhane’s T2 test (j (IIb)). Kruskal-Wallis test (h (GPX over-expression)). Two-way ANOVA with Bonferroni test (i, k). median (25% IQR, 75% IQR) (h (GPX over-expression)).
