Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation

Kyung Min Kim, Yoon Jung Choi, Jun Ha Hwang, A. Rum Kim, Hang Jun Cho, Eun Sook Hwang, Joong Yull Park, Sang Hoon Lee, Jeong-Ho Hong

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Shear stress activates cellular signaling involved in cellular proliferation, differentiation, and migration. However, the mechanisms of mesenchymal stem cell (MSC) differentiation under interstitial flow are not fully understood. Here, we show the increased osteogenic differentiation of MSCs under exposure to constant, extremely low shear stress created by osmotic pressure-induced flow in a microfluidic chip. The interstitial level of shear stress in the proposed microfluidic system stimulated nuclear localization of TAZ (transcriptional coactivator with PDZ-binding motif), a transcriptional modulator of MSCs, activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic differentiation. TAZ-depleted cells showed defects in shear stress-induced osteogenic differentiation. In shear stress induced cellular signaling, Rho signaling pathway was important forthe nuclear localization of TAZ. Taken together, these results suggest that TAZ is an important mediator of interstitial flow-driven shear stress signaling in osteoblast differentiation of MSCs.

Original languageEnglish
Article numbere92427
JournalPLoS One
Volume9
Issue number3
DOIs
Publication statusPublished - 2014 Mar 21

Fingerprint

Microfluidics
Stem cells
Mesenchymal Stromal Cells
shear stress
stem cells
Shear stress
Chemical activation
Osmotic Pressure
Osteoblasts
Cell signaling
Cell Differentiation
cell communication
Cell Proliferation
Genes
osteoblasts
osmotic pressure
cell differentiation
Modulators
cell proliferation
Defects

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation. / Kim, Kyung Min; Choi, Yoon Jung; Hwang, Jun Ha; Kim, A. Rum; Cho, Hang Jun; Hwang, Eun Sook; Park, Joong Yull; Lee, Sang Hoon; Hong, Jeong-Ho.

In: PLoS One, Vol. 9, No. 3, e92427, 21.03.2014.

Research output: Contribution to journalArticle

Kim, Kyung Min ; Choi, Yoon Jung ; Hwang, Jun Ha ; Kim, A. Rum ; Cho, Hang Jun ; Hwang, Eun Sook ; Park, Joong Yull ; Lee, Sang Hoon ; Hong, Jeong-Ho. / Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation. In: PLoS One. 2014 ; Vol. 9, No. 3.
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