Interestingly, we also found the upregulation level of EZH2 expression with increased H3K27me3 level in 2-year-old natural-aging mice (Fig. 6F, G and Supplementary Fig. 4b), suggesting the changes in EZH2 lead to the increase in H3K27me3 during the development of osteoarthritis. This evidence concerns the gene EZH2 and osteoarthritis.