Effect Of Genistein On The RANK/RANKL/OPG System Of BM-MSCs From RA Patients

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) from rheumatoid arthritis patients.Methods The cells were isolated and cultured by gradient centrifugation and adherence cultivation.The flow cytometer was used to identify the surface markers of the cells. BM-MSCs isolated and cultured from normal adults and rheumatoid arthritis patients were distributed into normal control group, Gen-treated group, E2-treated group and Gen+estrogen receptor antagonist group. Western blot was utilized to detect expression of RANK, RANKL and OPG, and immunofluorescence was applied to detect the distribution of estrogen receptora (ERa) in the BM-MSCs.Results The cells isolated and cultured were stable growth and phenotype homogeneous in vitro. The cells expressed CD29and CD90, but not CD34and CD45. The expression of RANK in BM-MSCs from RA patients is higher, otherwise the expression of OPG is lower, the RANKL/OPG ratio is higher. And similar to E2treated group, Gen could significantly up-regulate the expression of OPG but have no effects on the expression of RANK, RANKL, which resulted in significant decrease of the RANKL/OPG ratio. The results from immunofluorescence showed that Gen could facilitate ERa transferring into the nucleus.Conclusion Gen could regulate the expression and balance of RANKL/OPG in BM-MSCs from rheumatoid arthritis patients, and further modulate osteoclast and osteoblast differentiation, inhibit RA joint destruction and promote recovery of damaged joints through activating estrogen receptor mediated signal pathway.