Proteoglycans and Cartilage Repair
Repair of damaged articular cartilage in osteoarthritis (OA) is a clinical challenge. Because cartilage is an avascular and aneural tissue, normal mechanisms of tissue repair through recruitment of cells to the site of tissue destruction are not feasible. Proteoglycan (PG) depletion induced by the proinflammatory cytokine interleukin-1β, a principal mediator in OA, is a major factor in the onset and progression of joint destruction. Current symptomatic treatments of OA by anti-inflammatory drugs do not alter the progression of the disease. Various therapeutic strategies have been developed to antagonize the effect of proinflammatory cytokines. However, relatively few studies were conducted to stimulate anabolic activity, in an attempt to enhance cartilage repair. To this aim, a nonviral gene transfer strategy of glycosyltransferases responsible for PG synthesis has been developed and tested for its capacity to promote cartilage PG synthesis and deposition. Transfection of chondrocytes or cartilage explants by the expression vector for the glycosyltransferase β-1,3-glucuronosyltransferase-I (GlcAT-I) enhanced PG synthesis and deposition in the ECM by promoting the synthesis of chondroitin sulfate GAG chains of the cartilage matrix. This indicates that therapy mediated through GT gene delivery may constitute a new strategy for the treatment of OA.
Key wordsCartilage repair Chondrocytes Proteoglycans Osteoarthritis Glycosaminoglycan Gene transfer Glycosyltransferases
This work was supported by the Programme National de Recherches sur les Maladies Ostéo-Articulaires from the Institut National de la Santé et de la Recherche Médicale, The Agence Nationale de la Recherche (ANR BLAN08-3_313970), the Ligue Régionale contre le Cancer, and the Contrat de Programme de Recherche Clinique.
- 10.Venkatesan, N., Barré, L., Benani, A., Netter, P., Magdalou, J., Fournel-Gigleux, S., and Ouzzine, M. (2004). Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc. Natl. Acad. Sci. USA. 101, 18087–18092.PubMedCrossRefGoogle Scholar
- 11.Calabro, A., Midura, R., Wang, A., West, L., Plaas, A., and Hascall, V.C. (2001). Fluorophore-assisted carbohydrate electrophoresis (FACE) of glycosaminoglycans. Osteoarthritis Cartilage. 9 Suppl A, S16–S22.Google Scholar