title: Effect of focal adhesion kinase on the regulation of realignment and tenogenic differentiation of human mesenchymal stem cells by mechanical stretch.
abstract: Focal adhesion kinase (FAK) is a focal adhesion-associated protein kinase involved in cell adhesion and spreading. It is recruited as a participant in focal adhesion dynamics between cells and has a role in cell motility, differentiation, and survival. The role of FAK in the differentiation of human mesenchymal stem cells (hMSCs), however, is not well understood, particularly in terms of tenogenic differentiation. In this study, we reported that FAK regulates the mechanical stretch-induced realignment of hMSCs. We showed that FAK can be activated by mechanical stretch and, with a 10 μM PF 573228 (a novel small molecule inhibitor of FAK) treatment, FAK autophosphorylation at Tyr397 is significantly decreased. Moreover, our findings demonstrated that this decrease in FAK autophosphorylation at Tyr397 leads to the attenuation of upregulation of mechanical stretch-induced mRNA expression of tendon-related genes, including type I collagen, type III collagen, tenascin-C, and scleraxis. These results indicate that the FAK signaling molecule plays an important role in regulating cell realignment and tenogenic differentiation of hMSCs when induced by mechanical stretch. Collectively, our findings provide novel insight into the role of FAK in the realignment and mechanotransduction of hMSCs during the process of tenogenic differentiation induced by mechanical stretch.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, China.
authors.forename: Baiyao
authors.initials: B
authors.lastname: Xu
authors.forename: Guanbin
authors.initials: G
authors.lastname: Song
authors.forename: Yang
authors.initials: Y
authors.lastname: Ju
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology; D013314:Stress, Mechanical; D013450:Sulfones / Q000494:pharmacology; D019063:Tenascin / Q000096:biosynthesis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D024061:Collagen Type III; D051417:Focal Adhesion Kinase 1; D015363:Quinolones; D013450:Sulfones; D019063:Tenascin; C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; C093504:SCX protein, human