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Proteoglycans pp 339-355 | Cite as

Proteoglycans and Cartilage Repair

  • Mohamed OuzzineEmail author
  • Narayanan Venkatesan
  • Sylvie Fournel-Gigleux
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 836)

Abstract

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 words

Cartilage repair Chondrocytes Proteoglycans Osteoarthritis Glycosaminoglycan Gene transfer Glycosyltransferases 

Notes

Acknowledgments

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.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mohamed Ouzzine
    • 1
    Email author
  • Narayanan Venkatesan
    • 1
  • Sylvie Fournel-Gigleux
    • 1
  1. 1.UMR 7561 CNRS-Université Henri Poincaré Nancy IVandoeuvre-lès-NancyFrance

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