lovastatin reduces stemness via epigenetic reprograming of bmp2 and gata2 in human endometrium and endometriosis

background: objective: the stem cell theory in the endometriosis began the advanced avenue of targeting these cells as the novel therapy to eliminate endometriosis. in this regards, studies showed that lovastatin alters the cells from a stem-like state to a more differentiated condition and reduces the stemness. the aim of this study was to investigate whether lovastatin treatment could influence the expression and the methylation patterns of genes regulated the differentiation of endometrial mesenchymal stem cells (emscs) such as bmp2, gata2 and runx2 as well as the emscs markers. materials and methods: materials and methods: in this experimental investigation, mscs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. to investigate the osteogenic and adipogenic differentiation of emscs treated with the different concentration of lovastatin and decitabin, bmp2, runx2 and gata2 activities were measured by real time pcr. to determine the involvement of dna methylation in bmp2 and gata2 gene regulation of emscs, we used quantitative methylation specific pcr (qmsp) for evaluation of the bmp2 promoter status and the differentially methylated region of gata2 exon 4. results: results: in the present study, treatment with lovastatin increased the expression of bmp2 and runx2 and induced bmp2 promoter demethylation. we also demonstrated that lovastatin treatment downregulated gata2 expression via inducing of methylation. in addition, the results indicated that cd146 cell marker was decreased to 53% in response to lovastatin treatment comparing to untreated group. conclusion: conclusion: the findings indicated that lovastatin treatment could increase the differentiation of emscs toward the osteogenic and adiogenic lineage and decrease the expression of emscs markers and subsequently reduce the stemness.