DYNAMIC COMPRESSION REGULATES THE EXPRESSION AND SYNTHESIS OF CHONDROCYTE-SPECIFIC MATRIX MOLECULES IN BONE MARROW STROMAL CELLS

¹ George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia
² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia

^* To whom correspondence should be addressed. E-mail: levenston{at}gatech.edu.

	Abstract

The overall objective of the present study was to investigate the mechanotransduction of bovine bone marrow stromal cells (BMSCs) through the interactions between TGF-1, dexamethasone and dynamic compressive loading. Overall, the addition of TGF-1 increased cell viability, extracellular matrix (ECM) gene expression, matrix synthesis and sGAG construct content over basal media. 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 media 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 media supplements, with the samples treated with basal media being the least responsive and the samples treated with TGF-1 and dexamethasone being the most responsive at day 16. Both collagens I and II gene expressions were more responsive to dynamic loading than aggrecan expression. Dynamic compression upregulated Smad2/3 phosphorylation in samples treated with basal and TGF-1 media. These findings suggest that interactions between mechanical stimuli and TGF- signaling may an important mechanotransduction pathway for BMSCs, and indicate that mechanosensitivity may vary during the process of chondrogenesis.

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