title: RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for mechanical stretch-induced tenogenic differentiation of human mesenchymal stem cells.
abstract: Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to mechanical stretching. However, the means through which mechanical stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in mechanical stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated mechanical stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to mechanical stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses mechanical stretching and drives mechanical stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a stretch-induced environment and supports the therapeutic potential of hMSCs.
authors: Department of Mechanical Science and Engineering, Nagoya University, Nagoya, Japan.
authors: Baiyao
authors: B
authors: Xu
authors: Guanbin
authors: G
authors: Song
authors: Yang
authors: Y
authors: Ju
authors: Xian
authors: X
authors: Li
authors: Yuanhui
authors: Y
authors: Song
authors: Sachi
authors: S
authors: Watanabe
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D048430:Cell Shape; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013314:Stress, Mechanical; D013710:Tendons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; C066737:RHOA protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein