Crosstalk between Wnt/β-Catenin and Estrogen Receptor Signaling Synergistically Promotes Osteogenic Differentiation of Mesenchymal Progenitor Cells

摘要: Osteogenic differentiation from mesenchymal progenitor cells (MPCs) are initiated and regulated by a cascade of signaling events. Either Wnt/β-catenin or estrogen pathway has been shown to play an important role in regulating skeletal development maintaining adult tissue homeostasis. Here, we investigate the potential crosstalk synergy these two pathways osteogenic MPCs. We find that activation receptor (ER) estradiol (E2) exogenously expressed ERα MPCs synergistically enhances Wnt3A-induced early late markers, as well matrix mineralization. The E2 ERα-mediated can be effectively blocked antagonist tamoxifen. stimulation enhance endochondral ossification Wnt3A-transduced mouse fetal limb explants. Furthermore, significantly maturity mineralization subcutaneous intramuscular ectopic bone formation. Mechanistically, demonstrate does not exert any detectable effect on β-catenin/Tcf reporter activity. However, expression is up-regulated within first 48h AdWnt3A-transduced MPCs, whereas ERβ inhibited 24h. Moreover, key enzyme for biosynthesis estrogens aromatase modulated Wnt3A biphasic manner, at 24h but reduced after 48h. Our results that, while ER acts with promoting differentiation, may up-regulating down-regulating Thus, between should further explored therapeutic approach combating disorders, such fracture healing osteoporosis.