Diverse Roles of Integrin Receptors in Articular Cartilage

ISBN-13: 9783540787709 / Angielski / Miękka / 2008 / 62 str.

Mehdi Shakibaei; Constanze Csaki

Opis

1 Introduction Ar ticular cartilage is a specialised connective tissue with unique biological and mechanical properties which depend on the structural design of the tissue and the interactions between its unique resident cells, the chondrocytes, and the extrac- lular matrix (ECM) that makes up the bulk of the tissue (Buckwalter and Mankin 1998). Chondrocytes (Fig. 1 ) are the architects of the ECM (Muir 1995), building the macromolecular framework of the ECM from three distinct classes of mac- molecules: collagens, proteoglycans, and noncollagenous proteins. Of the collagens present in articular cartilage, collagens type II, IX, and XI form a fibrillar meshwork that gives cartilage tensile stiffness and strength (Eyre 2004; Buckwalter and Mankin 1998; Kuettner et al. 1991), whereas collagen type VI forms part of the matrix im- diately surrounding the chondrocytes, enabling them to attach to the macro- lecular framework of the ECM and acting as a transducer of biomechanical and biochemical signals in the articular cartilage (Guilak et al. 2006; Roughley and Lee 1994). Embedded in the collagen mesh are large aggregating proteoglycans (agg- can), which give cartilage its stiffness to compression, its resilience and contribute to its long-term durability (Dudhia 2005; Kiani et al. 2002; Luo et al. 2000; Roughley and Lee 1994). The extracellular matrix proteins in cartilage are of great significance for the regulation of the cell behaviour, proliferation, differentiation and morphogenesis (Kosher et al. 1973; Kosher and Church 1975; von der Mark et al. 1977; Hewitt et al.

Spis treści

Integrins in Articular Cartilage.- Concluding Remarks.

Blurb

Integrins belong to an evolutionary conserved family of adhesion molecules with important biological functions throughout the animal kingdom. They are heterodimeric glycoproteins involved in cell-cell and cell-matrix adhesion and communication. Physiologically they function as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumor cells. Integrin beta 1 (ß1-integrin) is a multi-functional member of the integrin superfamily and is an integral protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerization and receptor-mediated activity. The ß1-integrin family of cell surface receptors appears to play a major role in mediating cell-extracellular matrix interactions that are important in regulating these fundamental processes. ß1-integrins are important adhesion molecules that are highly expressed in articular chondrocytes where they bind to extracellular matrix molecules including fibronectin, laminin, and fibrillar collagens. In addition to mediating cell adhesion, members of the ß1 subfamily of integrins contribute to the organisation of the cytoskeleton and activate numerous intracellular signal transduction pathways. Recent studies from the authors' laboratory and from other leading groups have shown that ß1-integrins are essential for cell signalling and communication in chondrocytes. Furthermore, ß1-integrins function as mechanoreceptors in the chondrocyte mechanotransduction pathway. Their expression is therefore essential for maintaining the chondrocyte phenotype, preventing chondrocyte apoptosis and regulating chondrocyte-specific gene expression. This book volume summarizes the work that the authors have done on ß1-integrins over the last 18 years and focuses on the expression and regulation of these proteins in chondrocytes and their role in the context of the unique function of chondrocytes within articular cartilage.