a, b, Mouse articular chondrocytes in primary culture were treated for 36 h with MβCD-cholesterol, 25-HC or 7α,25-HC. Alternatively, chondrocytes were infected with 800 MOI of Ad-C, Ad-CH25H or Ad-CYP7B1. a, Relative mRNA levels (fold change against control) of the indicated molecules were quantified by qRT–PCR analysis (n = 6 biologically independent samples). b, Western blots of secreted MMP3 and MMP13 in the culture supernatants of chondrocytes (n = 5 biologically independent samples). c, Representative immunostaining of MMP3 and MMP13 in cartilage from sham- or DMM-operated wild-type and Ch25h−/− mice (left) and DMM-operated wild-type mice that received intra-articular injection of Ad-shControl or Ad-shCyp7b1 (right; n = 8 mice per group). d, e, Detection of aggrecan neoepitopes in the cartilage of mice that received intra-articular injection of Ad-C, Ad-CH25H or Ad-CYP7B1 (d; n = 8 mice per group) and sham- or DMM-operated mice fed regular diet or HCD (e, n = 10 mice per group). Means ± s.e.m. with two-tailed t-test. Exact P values (for P < 0.001) can be found in the accompanying Source Data. Scale bars, 25 μm.