Journal
FASEB JOURNAL
Volume 23, Issue 3, Pages 813-822Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-118166
Keywords
glycosyltransferases; proteoglycans; regulation; gene silencing
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Funding
- Institut National de la Sante et de la Recherche Medicale
- Agence Nationale de la Recherche (ANR) [BLAN08-3_313970]
- Ligue Regionale contre le Cancer
- Contrat de Programme de Recherche Clinique
- Programme Hospitalier de Recherche Clinique Centre Hospitalier Universitaire Nancy
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Osteoarthritis and rheumatoid arthritis are characterized by loss of proteoglycans (PGs) and their glycosaminoglycan (GAG) chains that are essential for cartilage function. Here, we investigated the role of glycosyltransferases (GTs) responsible for PG-GAG chain assembly during joint cartilage destruction and repair processes. At various times after antigen-induced arthritis (AIA) and papain-induced cartilage repair in rats, PG synthesis and deposition, expression of GTs, and GAG chain composition were analyzed. Our data showed that expression of the GT xylosyltransferase I (XT-I) gene initiating PG-GAG chain synthesis was significantly reduced in AIA rat cartilage and was associated with a decrease in PG synthesis. Interestingly, interleukin-1 beta, the main proinflammatory cytokine incriminated in joint diseases, down-regulated the XT-I gene expression with a concomitant decrease in PG synthesis in rat cartilage explants ex vivo. However, cartilage from papain-injected rat knees showed up-regulation of XT-I gene expression and increased PG synthesis at early stages of cartilage repair, a process associated with up-regulation of TGF-beta 1 gene expression and mediated by p38 mitogen-activated protein kinase activation. Consistently, silencing of XT-I expression by intraarticular injection of XT-I shRNA in rat knees prevented cartilage repair by decreasing PG synthesis and content. These findings show that GTs play a key role in the loss of PG-GAGs in joint diseases and identify novel targets for stimulating cartilage repair.-Venkatesan, N., Barre, L., Magdalou, J., Mainard, D., Netter, P., Fournel-Gigleux, S., Ouzzine, M. Modulation of xylosyltransferase I expression provides a mechanism regulating glycosaminoglycan chain synthesis during cartilage destruction and repair. FASEB J. 23, 813-822 (2009)
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