Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation

被引：155

作者：

Kim, Kyung Min ^{[1
]}

Choi, Yoon Jung ^{[2
]}

Hwang, Jun-Ha ^{[1
]}

Kim, A. Rum ^{[1
]}

Cho, Hang Jun ^{[1
]}

Hwang, Eun Sook ^{[3
,4
]}

Park, Joong Yull ^{[5
]}

Lee, Sang-Hoon ^{[2
]}

Hong, Jeong-Ho ^{[1
]}

机构：

[1] Korea Univ, Div Life Sci, Seoul, South Korea

[2] Korea Univ, Dept Biomed Engn, Seoul, South Korea

[3] Ewha Womans Univ, Coll Pharm, Seoul, South Korea

[4] Ewha Womans Univ, Global Top5 Res Program, Seoul, South Korea

[5] Chung Ang Univ, Coll Engn, Sch Mech Engn, Seoul 156756, South Korea

来源：

PLOS ONE | 2014年 / 9卷 / 03期

关键词：

SMOOTH-MUSCLE-CELLS; TRANSCRIPTIONAL COACTIVATOR; BONE; YAP; MECHANOTRANSDUCTION; ADIPOGENESIS; TRANSITION; INTERACTS; ENHANCER; CULTURE;

D O I：

10.1371/journal.pone.0092427

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：9

共 41 条

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