RGD Reference Report - Modulation of xylosyltransferase I expression provides a mechanism regulating glycosaminoglycan chain synthesis during cartilage destruction and repair. - Rat Genome Database

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Modulation of xylosyltransferase I expression provides a mechanism regulating glycosaminoglycan chain synthesis during cartilage destruction and repair.

Authors: Venkatesan, N  Barre, L  Magdalou, J  Mainard, D  Netter, P  Fournel-Gigleux, S  Ouzzine, M 
Citation: Venkatesan N, etal., FASEB J. 2009 Mar;23(3):813-22. Epub 2008 Nov 10.
RGD ID: 2313142
Pubmed: PMID:19001053   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.08-118166   (Journal Full-text)

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-1beta, 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-beta1 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
XYLT1HumanExperimental Arthritis  ISOXylt1 (Rattus norvegicus)mRNA:decreased expression:articular cartilageRGD 
Xylt1RatExperimental Arthritis  IEP mRNA:decreased expression:articular cartilageRGD 
Xylt1MouseExperimental Arthritis  ISOXylt1 (Rattus norvegicus)mRNA:decreased expression:articular cartilageRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Xylt1Ratproteoglycan biosynthetic process  IMP  RGD 
Xylt1Ratresponse to interleukin-1  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Xylt1  (xylosyltransferase 1)

Genes (Mus musculus)
Xylt1  (xylosyltransferase 1)

Genes (Homo sapiens)
XYLT1  (xylosyltransferase 1)


Additional Information