Effects of dietary sucrose and fat on the expression of metabolic and stress-response genes in knee cartilage. Effects of dietary sucrose and fat on the expression of metabolic and stress-response genes in knee cartilage. (A-D) Data are presented as expression relative to the geometric mean of three reference genes rather than as fold-change relative to the LFLS group, owing to the absence of longitudinal data for assessing diet-induced up- versus downregulation. Diet did not substantially alter the expression of cartilage anabolic genes (A) (e.g. Acan or Col2a1) or cartilage catabolic genes (B) (e.g. Adamts5 and Mmp13). However, diet did alter the expression of cellular stress mediators Foxo3, a transcription factor that positively regulates chondrocyte autophagy and antioxidant expression, and Ddit3 (i.e. Chop), a mediator of endoplasmic reticulum stress and the mitochondrial unfolded protein response. Further evaluation of genes involved in cellular proteostasis (C) and metabolism (D) showed significant effects of diet on mediators of cartilage mitochondrial proteostasis and lipid metabolism. Detailed cellular stress and metabolism gene expression data, including gene NCBI RefSeq numbers, are provided in Table S3. Lines over bars indicate statistically significant differences. *P<0.05, **P<0.01 and ***P<0.001 by one-way ANOVA and Tukey's multiple comparisons test or Kruskal–Wallis test with Dunn's multiple comparisons test; n=8 per diet group. Elise L. Donovan et al. Dis. Model. Mech. 2018;11:dmm034827 © 2018. Published by The Company of Biologists Ltd