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Ann Rheum Dis 67:iii75-iii82 doi:10.1136/ard.2008.098764
  • Osteoarthritis

Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism

  1. M B Goldring1,
  2. M Otero1,
  3. K Tsuchimochi1,
  4. K Ijiri2,
  5. Y Li3
  1. 1
    Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA
  2. 2
    Department of Orthopaedic Surgery, Graduate School of Medical and Dental Science, Kagoshima University, Japan
  3. 3
    Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA
  1. Dr M B Goldring, Hospital for Special Surgery, Caspary Research Building, Room 528, 535 East 70th Street, New York, NY 10021, USA; goldringm{at}hss.edu
  • Accepted 21 July 2008

Abstract

In osteoarthritis (OA), adult articular chondrocytes undergo phenotypic modulation in response to alterations in the environment owing to mechanical injury and inflammation. These processes not only stimulate the production of enzymes that degrade the cartilage matrix but also inhibit repair. With the use of in vitro and in vivo models, new genes, not known previously to act in cartilage, have been identified and their roles in chondrocyte differentiation during development and in dysregulated chondrocyte function in OA have been examined. These new genes include growth arrest and DNA damage (GADD)45β and the epithelial-specific ETS (ESE)-1 transcription factor, induced by bone morphogenetic protein (BMP)-2 and inflammatory cytokines, respectively. Both genes are induced by NF-κB, suppress COL2A1 and upregulate matrix meatalloproteinase-13 (MMP-13) expression. These genes have also been examined in mouse models of OA, in which discoidin domain receptor 2 is associated with MMP-13-mediated remodelling, in order to understand their roles in physiological cartilage homoeostasis and joint disease.

Footnotes

  • Funding: Work related to this review was supported by National Institutes of Health grant R01-AG022021 awarded to MBG and R01-AR051989 awarded to YL and Japan Society for the Promotion of Science (JSPS) grant 18591636 awarded to KI

  • Competing interests: None.