The Roles of Fibronectin Fragments in the Articular Chondrocytes: from Single Nucleotide Polymorphism to Functional Investigation

Degradation of articular cartilage is the important characteristics of osteoarthritis (OA). Catabolic factors mediating cartilage damage include proinflammatory cytokines, aggrecanases, matrix metalloproteinases, and nitric oxide. Recently, matrix degradation products generated by excessive proteolysis in arthritis have been found to mediate cartilage destruction. The catabolic activities of matrix degradation products, especially fibronectin fragments (FN-fs), are now been recognized and associated with cartilage damage. Splice variants of FN-fs to potentiate cartilage matrix damage through direct effects on chondrocytes are well established. Previous studies have shown that articular chondrocytes predominately express α1β1, α3β1, αVβ5 and α5β1 integrins. Fibronectin (FN) receptors containing the αV subunit and the classic receptor for fibronectin, integrin α5β1, seem to be important for the transmission of forces from extracellular matrix (ECM) to cells. Integrin-mediated pathways are at least partly responsible for these effects. In addition, fironectin fragments and interleukin-1beta have been shown to induce toll-like receptor (TLR) expression which contributes the progression of osteoarthritis. The beginning persuaded evidences from my laboratory and background rationale of the fibronectin prompted us to design this project entitled “The roles of fibronectin fragments in the articular chondrocytes: from single nucleotide polymorphism to functional investigation.” to explore in more detailed of the association of fibronectin, integrin and TLR gene functional polymorphisms and FN-fs in articular chondrocytes. SNPs are the most prevalent form of genetic variation within populations. Functional SNPs affect the structure or function of DNA and proteins and may affect the disease severity. This study will collect the knee joint sample with patients underwent total knee replacement in our hospital. The IRB has been approved. Cartilage tissue will be subjected to DNA extraction, primary cell culture, RNA and protein analysis, and functional investigation as well. This project will provide more understanding or find out the novelty for the role of fibronectin fragment in articular chondrocytes.