Abstract: Objective To explore the mechanism and effect of genistein (Gen)on receptor activator of nuclear factor kappa B (RANK),RANK ligand (RANKL)and osteoprotegerin (OPG)of mesenchymal stem cells (MSCs)in rheumatoid arthritis (RA)patients.Methods BM-MSCs isolated and cultured from normal adults and RA patients were divided into normal control group,Gen-treated group,E2-treated group and Gen +estrogen receptor antagonist group.Western blot was used to de-tect expression of RANK,RANKL and OPG,and immunofluorescence was used to detect the distribu-tion of estrogen receptorα(ERα)in BM-MSCs.Results According to result of Western blot,com-pared with normal adults,the expression of RANK in BM-MSCs from RA patients was higher,and the expression of OPG was lower,the RANKL/OPG ratio was higher.Similar to E2 treated group,Gen was able to significantly up-regulate the expression of OPG but show no effects on the expression of RANK, RANKL,which resulted in significant decrease of the RANKL/OPG ratio.The results from immunoflu-orescence showed that Gen could facilitate ERαtransferring into the nucleus.Conclusion Gen can regulate the expression and balance of RANKL/OPG in BM-MSCs in RA patients,and further modu-late osteoclast and osteoblast differentiation,inhibit RA joint destruction and promote recovery of dam-aged joints through activating estrogen receptor mediated signal pathway.