Activation of β-catenin stimulated by mechanical strain and estrogen requires estrogen receptor in mesenchymal stem cells (MSCs).

BACKGROUND AND OBJECTIVES Mechanical stimulation and hormones act via interconnected signaling pathways to influence the function of bone cells. Estrogen receptor (ER) and β-catenin play important role in bone formation and have implicated in mechanotransduction in bone cells. To investigate the interaction between mechanotransduction and estrogenic signaling in mesenchymal stem cells (MSCs), this study examined the effect of mechanical strain and estrogen on activation of β-catenin in MSCs, and the role of ER in response to mechanical strain and estrogen in MSCs. MATERIALS AND METHODS MSCs were exposed to mechanical strain (2%, 1 Hz) and estrogen (100 nM). The ER inhibitor, ICI182,780 was used to assess the role of ER in activation of β-catenin stimulated by mechanical strain and estrogen. Changes of activated β-catenin in the nuclei were determined by immunoflourescent test. The expression of β-catenin was detected by western blotting. RESULTS Mechanical strain and estrogen augment, respectively, activation of β-catenin and accumulation of activated β-catenin in the nuclei of MSCs. Combined treatment with estrogen and mechanical strain had higher levels of activated β-catenin than the cells exposed to mechanical strain or estrogen. After MSCs were pre-treated by ICI182,780, the level of activated β-catenin expression induced by mechanical strain or estrogen was depressed. Meanwhile, ICI182,780 blocked effect of combined stimulation on activation of β-catenin in MSCs. CONCLUSIONS Our study demonstrates that mechanical strain and estrogen both promote the levels of activated β-catenin in MSCs. Estrogen receptor implicates in activation of β-catenin stimulation by mechanical strain and estrogen in MSCs.