Extended Data Fig. 8: Repression of the Asparagine-mTORC1-HMGCR pathway in SkMCs leads to Coenzyme Q10 depletion, thereby contributing to Ferroptosis in the Quadriceps of OA joints. | Nature Aging

Extended Data Fig. 8: Repression of the Asparagine-mTORC1-HMGCR pathway in SkMCs leads to Coenzyme Q10 depletion, thereby contributing to Ferroptosis in the Quadriceps of OA joints.

From: Senescent macrophages induce ferroptosis in skeletal muscle and accelerate osteoarthritis-related muscle atrophy

Extended Data Fig. 8

(a) Scheme of Ferroptosis inhibitor Liproxstatin-1 intervention on mice. (b) Mean body weight of mice with or without Liproxstatin-1 treatment at different time points after DMM or Sham surgery (n = 10). (c) The LPO level of Quadriceps in mice with or without Liproxstatin-1 treatment at S12 and D12. (n = 5). (d) WGA staining and mean CSA analysis of Quadriceps in mice with or without Lip-1 treatment at S12 and D12 (n = 5). Scale bar=50 μm. (e) Scheme of untargeted metabolomics sequencing of Quadriceps. (f) The PLS-DA and (g) the heat map of the differential abundant metabolites (DAMs). (n = 5). (h) The top enriched signaling pathways of significantly differentially regulated metabolomics (DRMs) in the Quadriceps of mice between D12 vs S12. (i) The heat map of significantly different DAMs (p < 0.05). (j) Quantification of L-Asparagine in C2C12 cells stimulated with conditioned culture medium in vitro (n = 5), and in the Quadriceps of mice at S12 and D12 in vivo (n = 9 Sham, n = 8 DMM). (k-l) The quantitative results of western blotting analysis for the members involved in the mTOR single pathway in (k) the Quadriceps of mice at S12 and D12, and in (l) C2C12 cells under conditional medium stimulation. (n = 3). (m-n) The quantification of p-mTOR expression in western blotting analysis for quadriceps of mice with or without (m) L-Asp supplementation, or (n) D&Q intervention at S12 and D12. (n = 3). (o, p) The quantification of HMGCR expression in western blotting analysis for (o) Quadriceps of mice at S12 and D12, for (p) C2C12 cells under stimulation of conditional medium form macrophages, and for (q) Quadriceps of mice with or without HMGCR over-expression at S12 and D12 (n = 3). 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. Student’s t-test (j, k, l, o, p). One-way ANOVA with Bonferroni test (b, c, d, m, n, q). Two-way ANOVA (b).

Back to article page