Cross-talk between TGF-beta/SMAD and integrin signaling pathways in regulating hypertrophy of mesenchymal stem cell chondrogenesis under deferral dynamic compression

被引：108

作者：

Zhang, Tianting ^{[1
]}

Wen, Feng ^{[2
]}

Wu, Yingnan ^{[3
]}

Goh, Graham Seow Hng ^{[1
]}

Ge, Zigang ^{[4
]}

Tan, Lay Poh ^{[2
]}

Hui, James Hoi Po ^{[1
,5
]}

Yang, Zheng ^{[1
,5
]}

机构：

[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Orthopaed Surg, Singapore 119288, Singapore

[2] Nanyang Technol Univ, Sch Mat Sci & Engn, Singapore 639798, Singapore

[3] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 637459, Singapore

[4] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China

[5] Natl Univ Singapore, Inst Life Sci, Tissue Engn Program, Singapore 117510, Singapore

来源：

BIOMATERIALS | 2015年 / 38卷

基金：

英国医学研究理事会;

关键词：

Mesenchymal stem cells; Chondrogenesis; Dynamic compression; TGF/SMAD signaling; Integrin beta signaling; FOCAL ADHESION KINASE; MARROW STROMAL CELLS; ARTICULAR-CARTILAGE; MECHANICAL-PROPERTIES; MATRIX INTERACTIONS; GENE-EXPRESSION; SHEAR-STRESS; CHONDROCYTE; DIFFERENTIATION; SMAD;

D O I：

10.1016/j.biomaterials.2014.10.010

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

The molecular mechanisms of mechanotransduction in regulating mesenchymal stem cell (MSC) chondrogenesis are not fully understood and represent an area of growing investigation. In this study, human MSC was subjected to chondrogenic differentiation in chitosan-coated poly L-lactide-co-e-caprolactone scaffolds under free swelling or deferral dynamic compression conditions. The effect of deferral dynamic compression to MSC chondrogenesis and late stage hypertrophy development was investigated, and the involvement of TGF-beta/SMAD pathway and integrin beta 1 signaling was analyzed. Deferral dynamic compression enhanced cartilage formation and suppressed chondrocyte hypertrophy. Differential cell morphology and cytoskeletal organization were induced under dynamic compression, together with the activation of TGF-beta/Activin/Nodal and suppression of the BMP/GDP signaling. This was accompanied by the repression of integrin/FAK/ERK signaling in the non-hypertrophic cells when compared to the free swelling samples. Inhibition studies blocking TGF-beta/Activin/Nodal signaling heightened hypertrophy, activate BMP/SMAD1/5/8 and integrin signaling, while inhibition of integrin-ECM interaction suppressed hypertrophy and activate TGF-beta/SMAD2/3 in the free-swelling samples. This study demonstrates the roles of TGF-beta/SMAD and integrin signaling, and suggests cross-talk between these two signaling pathways, in regulating the compression-driven hypertrophy development. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：72 / 85

页数：14

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