a, Mice fed a regular diet (RD) or HCD were subjected to sham operation or DMM surgery. Left to right, safranin-O staining, scoring of cartilage destruction (OARSI grade), osteophyte maturity, subchondral bone plate (SBP) thickness (n = 10) and serum cholesterol levels (n = 5). b, c, Cholesterol levels in chondrocytes treated with IL-1β or TNFα for 36 h or infected for 36 h with Ad-C (800 MOI), Ad-HIF-2α or Ad-ZIP8 (b). Levels of Hif2a (also known as Epas1) and Zip8 (also known as Slc39a8) mRNA in adenovirus-infected chondrocytes (c). n = 8 each. d, Cholesterol levels in chondrocytes treated with IL-1β (5 ng ml−1) and the cholesterol synthesis inhibitors triparanol (TP) or atorvastatin (AV) for 36 h (n = 9). e, mRNA levels of proteins involved in cholesterol synthesis and efflux in chondrocytes treated with IL-1β or TNFα (n = 5) or in damaged regions of human OA (versus undamaged regions, n = 4) and DMM-operated cartilage (versus sham operation, n = 5). f, Characteristics of individuals with OA from whom cartilage samples were taken. g, Representative images (n = 5) of LOX1 expression, NBD-cholesterol uptake, and DIO-oxLDL uptake in chondrocytes treated with control or Lox1 siRNA with or without IL-1β or TNFα, or infected with 800 MOI of Ad-C, Ad-HIF-2α or Ad-ZIP8. Means ± 95% CI with Mann–Whitney U test for OARSI grade and osteophyte maturity; means ± s.e.m. with two-tailed t-test for SBP thickness and cholesterol levels (a). Means ± s.e.m. with one-way ANOVA and Bonferroni test (b, c, d) and means ± s.e.m. with two-tailed t-test (e). n indicates the number of biologically independent samples or mice per group. Exact P values (for P < 0.001) can be found in the accompanying Source Data. Scale bar, 25 μm.