Mechanosensitive TRPM7 mediates shear stress and modulates osteogenic differentiation of mesenchymal stromal cells through Osterix pathway

• DOI: 10.1038/srep16522
• Publication Date: 2015-11-12T11:40:17Z
• Authors: Yi-Shiuan Liu; Yu-An Liu; Chin-Jing Huang; Meng-Hua Yen; Chien-Tzu Tseng; Shu Chien; Oscar K. Lee
• Keywords: Mechanotransduction; Intramembranous ossification; Endochondral ossification; TRPM7; RUNX2

Abstract Microenvironments that modulate fate commitments of mesenchymal stromal cells (MSCs) are composed chemical and physical cues, but the latter ones much less investigated. Here we demonstrate intermittent fluid shear stress (IFSS), a potent physiologically relevant mechanical stimulus, regulates osteogenic differentiation MSCs through Transient receptor potential melastatin 7 (TRPM7)-Osterix axis. Immunostaining showed localization TRPM7 near or at cell membrane upon IFSS calcium imaging analysis demonstrated transient increase cytosolic free calcium. Expressions marker genes including Osterix, not Runx2, were upregulated after three-hour IFSS. Phosphorylation p38 Smad1/5 was promoted by as well. gene knockdown abolished promotion bone-related expressions phosphorylation. We illustrate is mechanosensitive to force 1.2 Pa, which lower than 98 Pa pressure loading reported recently mediates distinct mechanotransduction pathways. Additionally, our results suggest differential roles in endochondral intramembranous ossification. Together, this study elucidates displays an efficient mechano-modulation for differentiation. Such findings should be taken into consideration when designing scaffolds microfluidic devices induction future.