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Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells.

Publication ,  Journal Article
Shih, Y-RV; Tseng, K-F; Lai, H-Y; Lin, C-H; Lee, OK
Published in: J Bone Miner Res
April 2011

Mesenchymal stem cells (MSCs) cultured on extracellular matrices with different stiffness have been shown to possess diverse lineage commitment owing to the extracellular mechanical stimuli sensed by the cells. The aim of this study was to further delineate how matrix stiffness affects intracellular signaling through the mechanotransducers Rho kinase (ROCK) and focal adhesion kinase (FAK) and subsequently regulates the osteogenic phenotype of MSCs. MSCs were cultured in osteogenic medium on tunable polyacrylamide hydrogels coated with type I collagen with elasticities corresponding to Young's modulus of 7.0 ± 1.2 and 42.1 ± 3.2 kPa. Osteogenic differentiation was increased on stiffer matrices, as evident by type I collagen, osteocalcin, and Runx2 gene expressions and alizarin red S staining for mineralization. Western blot analysis demonstrated an increase in kinase activities of ROCK, FAK, and ERK1/2 on stiffer matrices. Inhibition of FAK, an important mediator of osteogenic differentiation, and inhibition of ROCK, a known mechanotransducer of matrix stiffness during osteogenesis, resulted in decreased expression of osteogenic markers during osteogenic induction. In addition, FAK affects osteogenic differentiation through ERK1/2, whereas ROCK regulates both FAK and ERK1/2. Furthermore, α(2)-integrin was upregulated on stiffer matrices during osteogenic induction, and its knockdown by siRNA downregulated the osteogenic phenotype through ROCK, FAK, and ERK1/2. Taken together, our results provide evidence that the matrix rigidity affects the osteogenic outcome of MSCs through mechanotransduction events that are mediated by α(2)-integrin.

Duke Scholars

Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

April 2011

Volume

26

Issue

4

Start / End Page

730 / 738

Location

United States

Related Subject Headings

  • rho-Associated Kinases
  • beta Catenin
  • RNA, Small Interfering
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Osteogenesis
  • Osteocalcin
  • Osteoblasts
  • Myosin-Light-Chain Phosphatase
  • Mitogen-Activated Protein Kinase 3
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shih, Y.-R., Tseng, K.-F., Lai, H.-Y., Lin, C.-H., & Lee, O. K. (2011). Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res, 26(4), 730–738. https://doi.org/10.1002/jbmr.278
Shih, Yu-Ru V., Kuo-Fung Tseng, Hsiu-Yu Lai, Chi-Hung Lin, and Oscar K. Lee. “Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells.J Bone Miner Res 26, no. 4 (April 2011): 730–38. https://doi.org/10.1002/jbmr.278.
Shih Y-RV, Tseng K-F, Lai H-Y, Lin C-H, Lee OK. Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res. 2011 Apr;26(4):730–8.
Shih, Yu-Ru V., et al. “Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells.J Bone Miner Res, vol. 26, no. 4, Apr. 2011, pp. 730–38. Pubmed, doi:10.1002/jbmr.278.
Shih Y-RV, Tseng K-F, Lai H-Y, Lin C-H, Lee OK. Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells. J Bone Miner Res. 2011 Apr;26(4):730–738.
Journal cover image

Published In

J Bone Miner Res

DOI

EISSN

1523-4681

Publication Date

April 2011

Volume

26

Issue

4

Start / End Page

730 / 738

Location

United States

Related Subject Headings

  • rho-Associated Kinases
  • beta Catenin
  • RNA, Small Interfering
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Osteogenesis
  • Osteocalcin
  • Osteoblasts
  • Myosin-Light-Chain Phosphatase
  • Mitogen-Activated Protein Kinase 3