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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/C38    most recent 00548.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gill, K. S. Articles by Goldberg, H. A. Search for Related Content PubMed PubMed Citation Articles by Gill, K. S. Articles by Goldberg, H. A.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Rho-ROCK signaling differentially regulates chondrocyte spreading on fibronectin and bone sialoprotein

CIHR Group in Skeletal Development and Remodeling, ¹Department of Biochemistry, ²Department of Physiology and Pharmacology, and ³Division of Oral Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

Submitted 19 November 2007 ; accepted in final form 1 May 2008

The mammalian growth plate is a dynamic structure rich in extracellular matrix (ECM). Interactions of growth plate chondrocytes with ECM proteins regulate cell behavior. In this study, we compared chondrocyte adhesion and spreading dynamics on fibronectin (FN) and bone sialoprotein (BSP). Chondrocyte adhesion and spreading were also compared with fibroblasts to analyze potential cell-type-specific effects. Chondrocyte adhesion to BSP is independent of posttranslational modifications but is dependent on the RGD sequence in BSP. Whereas chondrocytes and fibroblasts adhered at similar levels on FN and BSP, cells displayed more actin-dependent spread on FN despite a 16x molar excess of BSP adsorbed to plastic. To identify intracellular mediators responsible for this difference in spreading, we investigated focal adhesion kinase (FAK)-Src and Rho-Rho kinase (ROCK) signaling. Although activated FAK localized to the vertices of adhered chondrocytes, levels of FAK activation did not correlate with the extent of spreading. Furthermore, Src inhibition reduced chondrocyte spreading on both FN and BSP, suggesting that FAK-Src signaling is not responsible for less cell spreading on BSP. In contrast, inhibition of Rho and ROCK in chondrocytes increased cell spreading on BSP and membrane protrusiveness on FN but did not affect cell adhesion. In fibroblasts, Rho inhibition increased fibroblast spreading on BSP while ROCK inhibition changed membrane protrusiveness of FN and BSP. In summary, we identify a novel role for Rho-ROCK signaling in regulating chondrocyte spreading and demonstrate both cell- and matrix molecule-specific mechanisms controlling cell spreading.

fibroblast; cell adhesion; focal adhesion kinase; arginine-glycine-aspartate