YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK
While yes-associated protein (YAP) is now recognized as a potent mechanosensitive transcriptional regulator to affect cell growth and differentiation including the osteogenic transcription of mesenchymal stem cells (MSCs), most studies have reported the YAP mechanosensing of static mechanophysical c...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1306002/full |
| _version_ | 1797357471627476992 |
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| author | Eunju Kim Brandon D. Riehl Tasneem Bouzid Ruiguo Yang Bin Duan Bin Duan Henry J. Donahue Jung Yul Lim |
| author_facet | Eunju Kim Brandon D. Riehl Tasneem Bouzid Ruiguo Yang Bin Duan Bin Duan Henry J. Donahue Jung Yul Lim |
| author_sort | Eunju Kim |
| collection | DOAJ |
| description | While yes-associated protein (YAP) is now recognized as a potent mechanosensitive transcriptional regulator to affect cell growth and differentiation including the osteogenic transcription of mesenchymal stem cells (MSCs), most studies have reported the YAP mechanosensing of static mechanophysical cues such as substrate stiffness. We tested MSC response to dynamic loading, i.e., cyclic mechanical stretching, and assessed YAP mechanosensing and resultant MSC osteogenesis. We showed that cyclic stretching at 10% strain and 1 Hz frequency triggered YAP nuclear import in MSCs. YAP phosphorylation at S127 and S397, which is required for YAP cytoplasmic retention, was suppressed by cyclic stretch. We also observed that anti-YAP-regulatory Hippo pathway, LATS phosphorylation, was significantly decreased by stretch. We confirmed the stretch induction of MSC osteogenic transcription and differentiation, and this was impaired under YAP siRNA suggesting a key role of YAP dynamic mechanosensing in MSC osteogenesis. As an underlying mechanism, we showed that the YAP nuclear transport by cyclic stretch was abrogated by ROCK inhibitor, Y27632. ROCK inhibitor also impaired the stretch induction of F-actin formation and MSC osteogenesis, thus implicating the role of the ROCK-F-actin cascade in stretch-YAP dynamic mechanosensing-MSC osteogenesis. Our results provide insight into bone tissue engineering and skeletal regenerative capacity of MSCs especially as regards the role of dynamic mechanical loading control of YAP-mediated MSC osteogenic transcription. |
| first_indexed | 2024-03-08T14:45:38Z |
| format | Article |
| id | doaj.art-0ea91f81e5aa48959c8b8d7f98311a99 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-03-08T14:45:38Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-0ea91f81e5aa48959c8b8d7f98311a992024-01-11T10:16:12ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852024-01-011110.3389/fbioe.2023.13060021306002YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCKEunju Kim0Brandon D. Riehl1Tasneem Bouzid2Ruiguo Yang3Bin Duan4Bin Duan5Henry J. Donahue6Jung Yul Lim7Department of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesDepartment of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Mechanical and Materials Engineering, College of Engineering, University of Nebraska-Lincoln, Lincoln, NE, United StatesWhile yes-associated protein (YAP) is now recognized as a potent mechanosensitive transcriptional regulator to affect cell growth and differentiation including the osteogenic transcription of mesenchymal stem cells (MSCs), most studies have reported the YAP mechanosensing of static mechanophysical cues such as substrate stiffness. We tested MSC response to dynamic loading, i.e., cyclic mechanical stretching, and assessed YAP mechanosensing and resultant MSC osteogenesis. We showed that cyclic stretching at 10% strain and 1 Hz frequency triggered YAP nuclear import in MSCs. YAP phosphorylation at S127 and S397, which is required for YAP cytoplasmic retention, was suppressed by cyclic stretch. We also observed that anti-YAP-regulatory Hippo pathway, LATS phosphorylation, was significantly decreased by stretch. We confirmed the stretch induction of MSC osteogenic transcription and differentiation, and this was impaired under YAP siRNA suggesting a key role of YAP dynamic mechanosensing in MSC osteogenesis. As an underlying mechanism, we showed that the YAP nuclear transport by cyclic stretch was abrogated by ROCK inhibitor, Y27632. ROCK inhibitor also impaired the stretch induction of F-actin formation and MSC osteogenesis, thus implicating the role of the ROCK-F-actin cascade in stretch-YAP dynamic mechanosensing-MSC osteogenesis. Our results provide insight into bone tissue engineering and skeletal regenerative capacity of MSCs especially as regards the role of dynamic mechanical loading control of YAP-mediated MSC osteogenic transcription.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1306002/fullmechanical stretch loadingmesenchymal stem cellosteogenesisYAPHippoROCK |
| spellingShingle | Eunju Kim Brandon D. Riehl Tasneem Bouzid Ruiguo Yang Bin Duan Bin Duan Henry J. Donahue Jung Yul Lim YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK Frontiers in Bioengineering and Biotechnology mechanical stretch loading mesenchymal stem cell osteogenesis YAP Hippo ROCK |
| title | YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK |
| title_full | YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK |
| title_fullStr | YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK |
| title_full_unstemmed | YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK |
| title_short | YAP mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by ROCK |
| title_sort | yap mechanotransduction under cyclic mechanical stretch loading for mesenchymal stem cell osteogenesis is regulated by rock |
| topic | mechanical stretch loading mesenchymal stem cell osteogenesis YAP Hippo ROCK |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1306002/full |
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