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

Min Tang,Jirui Wen,Xinghong Yao,Mingyue Bao,Liang Li,Xueling He

doi:10.32604/biocell.2022.018967

Abstract

The present study was designed to investigate the role of estrogen receptor α (ERα) in biaxial tensile strain (BTS) regulated osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). rBMSCs were derived from rats and overexpressed ERα. The rBMSCs were subjected to BTS at 1 Hz with a strain of 2% for 4 h per day, 3 days, with or without ERα inhibitor ICI 182,780 (ICI). Then, bone mineralization was performed by Alizarin Red Staining. The markers of osteogenic differentiation and downstream Wnt3a/β-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) α (ERα), Wnt3a, and β-catenin. BTS The activated Wnt3a/β-catenin signaling pathway induced by BTS was abolished by ICI 182,780 (ICI). In addition, overexpressing ERα in rBMSCs promoted the osteogenic differentiation by BTS. Taken together, BTS induced osteogenic differentiation of rBMSCs via the ERα and downstream canonical Wnt3a/β-catenin pathway.

Highlights

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, increased bone fragility and fracture risk due to the destruction of bone microstructures
Because the role of estrogen receptor α (ERα) in stretch-induced osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) was still uncertain, to test whether biaxial tensile strain (BTS) regulates the osteogenic differentiation of rBMSCs via ERαcanonical Wnt pathway, we evaluate the effects of ERα-canonical Wnt pathway on BTS-induced osteogenic differentiation of rBMSCs by ERα inhibitor and overexpressing ERα
Mechanical strain induces the osteogenic differentiation of rBMSCs our previous study has confirmed that tensile strain can up-regulate the mRNA expression levels of Runx2 and collagen type I (Col I) of rBMSCs (Li et al, 2013), the optimal mechanical strain were ascertained in this study

Summary

Introduction

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass, increased bone fragility and fracture risk due to the destruction of bone microstructures. There are far more women than men in osteoporosis patients, especially postmenopausal women. The decrease in estrogen level is the main cause of postmenopausal osteoporosis (Sharma et al, 2018). The expression of estrogen receptor (ER), especially ERα, is regulated by the hormone levels in vivo (Khalid and Krum, 2016). With the decrease of estrogen level in postmenopausal women, the number and function of ERα on osteocytes reduce, which significantly increases the incidence of osteoporosis in postmenopausal women (Lanyon et al, 2004). Recent studies had found that estrogen receptors could interact with some signaling pathways in cells through phosphorylation to activate themselves in an estrogen-independent manner

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Conclusion