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TISSUE-SPECIFIC STEM CELLS

Dynamic Compression Regulates the Expression and Synthesis of Chondrocyte-Specific Matrix Molecules in Bone Marrow Stromal Cells

^aGeorge W. Woodruff School of Mechanical Engineering,
^bWallace H. Coulter Department of Biomedical Engineering, and
^cParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA

Key Words. Chondrogenesis • Signal transduction • Mechanical • Transforming growth factor β • Stromal cells

Correspondence: Marc E. Levenston, Ph.D., Biomechanical Engineering, Mechanical Engineering Department, Stanford University, 231 Durand Building, Stanford, California 94305-4038, USA. Telephone: 650-723-9464; Fax: 650-725-1587; e-mail: levenston{at}stanford.edu

Received July 17, 2006; accepted for publication November 15, 2006.
First published online in STEM CELLS EXPRESS   November 22, 2006.



The overall objective of the present study was to investigate the mechanotransduction of bovine bone marrow stromal cells (BMSCs) through the interactions between transforming growth factor β1 (TGF-β1), dexamethasone, and dynamic compressive loading. Overall, the addition of TGF-β1 increased cell viability, extracellular matrix (ECM) gene expression, matrix synthesis, and sulfated glycosaminoglycan content over basal construct medium. The addition of dexamethasone further enhanced extracellular matrix gene expression and protein synthesis. There was little stimulation of ECM gene expression or matrix synthesis in any medium group by mechanical loading introduced on day 8. In contrast, there was significant stimulation of ECM gene expression and matrix synthesis in chondrogenic media by dynamic loading introduced on day 16. The level of stimulation was also dependent on the medium supplements, with the samples treated with basal medium being the least responsive and the samples treated with TGF-β1 and dexamethasone being the most responsive at day 16. Both collagen I and collagen II gene expressions were more responsive to dynamic loading than aggrecan gene expression. Dynamic compression upregulated Smad2/3 phosphorylation in samples treated with basal and TGF-β1 media. These findings suggest that interactions between mechanical stimuli and TGF-β signaling may be an important mechanotransduction pathway for BMSCs, and they indicate that mechanosensitivity may vary during the process of chondrogenesis.

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