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

doi:10.1371/journal.pone.0092427

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

PLoS One. 2014 Mar 21;9(3):e92427. doi: 10.1371/journal.pone.0092427. eCollection 2014.

Authors

Kyung Min Kim¹, Yoon Jung Choi², Jun-Ha Hwang¹, A Rum Kim¹, Hang Jun Cho¹, Eun Sook Hwang³, Joong Yull Park⁴, Sang-Hoon Lee², Jeong-Ho Hong¹

Affiliations

¹ Division of Life Sciences, Korea University, Seoul, Republic of Korea.
² Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
³ College of Pharmacy and Global Top5 Research Program, Ewha Womans University, Seoul, Republic of Korea.
⁴ School of Mechanical Engineering, College of Engineering, Chung-Ang University, Seoul, Republic of Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / physiology
Cells, Cultured
Humans
Intracellular Signaling Peptides and Proteins / biosynthesis
Intracellular Signaling Peptides and Proteins / metabolism*
Mesenchymal Stem Cells / cytology*
Microfluidics
Osteoblasts / physiology
Osteogenesis / physiology*
Rho Factor / metabolism
Shear Strength
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
rho GTP-Binding Proteins

Substances

Intracellular Signaling Peptides and Proteins
Rho Factor
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human
rho GTP-Binding Proteins

Grants and funding

This work was supported by the Industrial Core Technology Development Program funded by the Ministry of Knowledge Economy (No. 10041913) and a grant from the Korea Healthcare Technology R&D project, Ministry for Health & Welfare (A120349 & A120476), Republic of Korea. J. Y. P. is supported by the Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology, Republic of Korea (2012R1A1A1015181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.