a–c, Microarray analysis of cholesterol metabolism-related genes in chondrocytes treated with IL-1β, Ad-C (control), Ad-HIF-2α or Ad-ZIP8. a, Fold changes in mRNA levels versus those in vehicle or Ad-C-infected cells (n = 4). b, Heat maps (left, IL-1β; centre, Ad-HIF-2α; right, Ad-ZIP8) of genes involved in cholesterol metabolism and metabolic pathways of bile acid synthesis in the liver. c, PPI network based on CH25H and CYP7B1. Nodes and links represent protein-encoding genes and their interactions, respectively. Genes shown in red and blue indicate those annotated as upregulated and downregulated, respectively, in the PPI network. d, e, mRNA levels (d) and representative RT–PCR gel images (e) in chondrocytes treated with IL-1β or TNFα, or infected with Ad-C (800 MOI; left), Ad-HIF-2α (middle) or Ad-ZIP8 (right; n = 5). f, Safranin-O staining and immunostaining of the indicated proteins in mice that underwent intra-articular injection of Ad-HIF-2α or Ad-ZIP8 (n = 7). Means ± s.e.m. with one-way ANOVA and Bonferroni test. 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. For gel source data, see Supplementary Fig. 1. Scale bars, 25 μm.