Suprastructural specificity of integrin-mediated cell-matrix-interactions: Relation to cartilage homeostasis and osteoarthritis

• Applicants: Professor Dr. Peter Bruckner; Professor Dr. Johannes Andreas Eble
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190050141

Integrins are heterodimeric cell surface-receptors and mediate mechanical and signalling interactions of chondrocytes with the extracellular matrix which are crucial for cellular functions and, hence, tissue homeostasis. In cartilage, the substrate of integrins is a composite consisting of two discrete suprastructural compartments, the proteoglycan matrix and the D-banded fibrils. Although modulated by the extrafibrillar matrix, the fibrils probably are the prime target of integrin binding. Cartilage fibrils comprise several types of collagen molecules amalgamated into suprastructures with distinct organizations. In addition, non-collagenous molecules at the fibril periphery modulate fibril surfaces. For these reasons, physiologically relevant integrin binding epitopes do not necessarily reside in single matrix macromolecules but, rather, in supramolecular arrays. In most studies on cell-matrix-interactions, this is not taken into account. Therefore binding of integrins to aggregated matrix ligands and its consequences on chondrocyte activities will be investigated here. We hypothesize that progression of late chondrocyte differentiation as well as matrix synthesis and remodelling are controlled by discrete supramolecular matrix-to-cell-interactions that, hence, are vital prerequisites for articular cartilage functions and prevention of degenerative joint disease.

• DFG Programme: Research Grants
• Participating Person: Dr. Uwe Hansen