Among these genes, Acp5, Ctsk, and Mmp9 were widely known to play critical roles in regulating RA pathogenesis and osteoclast function (Fig. 5b).29,30 Hydroxymethylated DNA immunoprecipitation with qPCR (hMeDIP-qPCR) analysis demonstrated that OI robustly suppressed DNA demethylation at the promoter regions of Acp5, Ctsk, and Mmp9 on the third day of osteoclast differentiation (Fig. S9d). This evidence concerns the gene MMP9 and rheumatoid arthritis.