Cyclic biaxial tensile strain enhances osteogenic differentiation in rat bone marrow-derived mesenchymal stem cells via activating ER alpha-Wnt3a/beta-catenin pathway

The present study was designed to investigate the role of estrogen receptor alpha (ER alpha) in biaxial tensile strain (BTS) regulated osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). rBMSCs were derived fromrats and overexpressed ER alpha. The rBMSCs were subjected to BTS at 1Hz with a strain of 2% for 4 h per day, 3 days, with or without ER alpha inhibitor ICI 182,780 (ICI). Then, bone mineralization was performed by Alizarin Red Staining. The markers of osteogenic differentiation and downstream Wnt3a/beta-catenin signaling were detected by western blotting. Results showed that BTS enhanced the osteogenic differentiation of rBMSCs, increased protein expression levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), collagen type I (Col I) and osteocalcin (OCN), and it increased the protein expression levels of estrogen receptor (ER) alpha (ER alpha), Wnt3a, and beta-catenin. BTS The activated Wnt3a/beta-catenin signaling pathway induced by BTS was abolished by ICI 182,780 (ICI). In addition, overexpressing ERa in rBMSCs promoted the osteogenic differentiation by BTS. Taken together, BTS induced osteogenic differentiation of rBMSCs via the ER alpha and downstream canonical Wnt3a/beta-catenin pathway.