HIF-1α-TWIST pathway restrains cyclic mechanical stretch-induced osteogenic differentiation of bone marrow mesenchymal stem cells. (2nd November 2019)

• Record Type: Journal Article
• Authors: Liu, Ying; Huang, Xia; Yu, Haibo; Yang, Jing; Li, Yazhen; Yuan, Xiao; Guo, Qingyuan
• Is Part Of: Connective tissue research. Volume 60:Number 6(2019)
• Page Start: 544
• Page End: 554
• Publication Date: 2019-11-02
• Subjects: Bone mesenchymal stem cells (BMSCs) -- cyclic mechanical stretch -- osteogenic differentiation -- HIF-1α-TWIST pathway; Connective tissues -- Periodicals; 616.770072
• DOI: 10.1080/03008207.2019.1601185
• Languages: English
• ISSNs: 0300-8207

Abstract

ABSTRACT: Aim : Mechanical strain plays a crucial role in bone formation and remodeling. Hypoxia-inducible factor (HIF)-1α and TWIST are upstream of master regulators of osteogenesis, including runt-related transcription factor 2 (RUNX2) and bone morphogenetic proteins (BMPs). This study investigated the effect of the HIF-1α-TWIST pathway on cyclic mechanical stretch-induced osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism. Materials and Methods : BMSCs were isolated from bone marrow derived from the femurs and humeri of Sprague-Dawley rats. Osteogenic differentiation of BMSCs was induced by applying cyclic mechanical stretch using the Flexcell Tension System. HIF-1α and TWIST were knocked down using recombinant lentiviral vectors. Osteogenic differentiation was evaluated by real-time qPCR, western blotting, and the alkaline phosphatase (ALP) activity assay. Results : Cyclic mechanical stretch increased ALP activity and expression of HIF-1α and TWIST in BMSCs. Knockdown of HIF-1α decreased TWIST expression in stretched BMSCs. Moreover, knockdown of HIF-1α or TWIST enhanced cyclic mechanical stretch-induced osteogenic differentiation of BMSCs. In addition, knockdown of TWIST increased expression of RUNX2 and BMP2 in stretched BMSCs. Conclusions : The HIF-1α-TWIST signaling pathway inhibits cyclic mechanical stretch-induced osteogenic differentiation of BMSCs. This finding may facilitate cell and tissue engineering for clinical applications.