NDLI: Bone morphogenetic protein-2-induced signaling and osteogenesis is regulated by cell shape, RhoA/ROCK, and cytoskeletal tension.

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Bone morphogenetic protein-2-induced signaling and osteogenesis is regulated by cell shape, RhoA/ROCK, and cytoskeletal tension.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Yang-Kao Yu, Xiang Cohen, Daniel M. Wozniak, Michele A. Yang, Michael T. Gao, Lin Eyckmans, Jeroen Chen, Christopher S.
Description	Country affiliation: United States Author Affiliation: Wang YK ( Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.)
Abstract	Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is classically thought to be mediated by different cytokines such as the bone morphogenetic proteins (BMPs). Here, we report that cell adhesion to extracellular matrix (ECM), and its effects on cell shape and cytoskeletal mechanics, regulates BMP-induced signaling and osteogenic differentiation of hMSCs. Using micropatterned substrates to progressively restrict cell spreading and flattening against ECM, we demonstrated that BMP-induced osteogenesis is progressively antagonized with decreased cell spreading. BMP triggered rapid and sustained RhoA/Rho-associated protein kinase (ROCK) activity and contractile tension only in spread cells, and this signaling was required for BMP-induced osteogenesis. Exploring the molecular basis for this effect, we found that restricting cell spreading, reducing ROCK signaling, or inhibiting cytoskeletal tension prevented BMP-induced SMA/mothers against decapentaplegic (SMAD)1 c-terminal phosphorylation, SMAD1 dimerization with SMAD4, and SMAD1 translocation into the nucleus. Together, these findings demonstrate the direct involvement of cell spreading and RhoA/ROCK-mediated cytoskeletal tension generation in BMP-induced signaling and early stages of in vitro osteogenesis, and highlight the essential interplay between biochemical and mechanical cues in stem cell differentiation.
File Format	HTM / HTML
ISSN	15473287
e-ISSN	15578534
DOI	10.1089/scd.2011.0293
Journal	Stem Cells and Development
Issue Number	7
Volume Number	21
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2012-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Discipline Hematology Bone Morphogenetic Protein 2 Physiology Cell Shape Osteogenesis Signal Transduction Stress Fibers Metabolism Active Transport, Cell Nucleus Cell Adhesion Cell Differentiation Cells, Cultured Cytoskeleton Extracellular Matrix Gene Expression Mesenchymal Stromal Cells Myosins Phosphorylation Smad Proteins Stress, Mechanical Rho-associated Kinases Rhoa Gtp-binding Protein Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Hematology

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