title: Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes.
abstract: BACKGROUND
  Members of the ephrin system, the ephrin receptor erythropoietin-producing hepatocellular B4 (EphB4) and its specific ligand, ephrin B2, appear to be involved in the bone remodelling process. We recently showed that their interaction inhibits the resorptive activity of human osteoarthritic (OA) subchondral bone osteoblasts. Hence, we further investigated the possible implication of these ephrin members on the catabolic/anabolic activities of human OA chondrocytes.
  
  
  METHODS
  EphB4 receptor and ephrin B2 levels were determined by quantitative PCR and immunohistochemistry, and the effects of ephrin B2 on the expression/production of factors involved in the OA process.
  
  
  RESULTS
  EphB4 receptors and ephrin B2 ligands are expressed and produced by human normal and OA chondrocytes. Ephrin B2 protein was found at similar levels in both cartilage types, whereas EphB4 receptor expression (P < 0.0001) and production (P < 0.01) levels were significantly increased in OA chondrocytes/cartilage. Ephrin B2 treatment significantly inhibited the interleukin (IL)-1beta, IL-6, matrix metalloproteinase-1 (MMP-1), MMP-9, MMP-13, and proteinase-activated receptor-2 (PAR-2) gene expression levels, whereas MMP-2 was unaffected, and significantly increased collagen type II, a cartilage specific macromolecule. It also inhibited the IL-1beta stimulated protein production of IL-6, MMP-1 and MMP-13.
  
  
  CONCLUSIONS
  Our study is the first to provide data on the presence and role of ephrin B2/EphB4 receptors in human chondrocytes/cartilage. Data showed that ephrin B2 treatment positively impacts the abnormal metabolism of OA cartilage by inhibiting important catabolic factors involved in this disease at the same time as increasing anabolic activity.
authors: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec, Canada. kwantats@yahoo.fr
authors: Steeve
authors: S
authors: Kwan Tat
authors: Jean-Pierre
authors: JP
authors: Pelletier
authors: Nathalie
authors: N
authors: Amiable
authors: Christelle
authors: C
authors: Boileau
authors: Martin
authors: M
authors: Lavigne
authors: Johanne
authors: J
authors: Martel-Pelletier
mesh_terms: D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D036388:Ephrin-B2 / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D010003:Osteoarthritis / Q000378:metabolism*; D036224:Receptor, EphB4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D036388:Ephrin-B2; D053583:Interleukin-1beta; D015850:Interleukin-6; D036224:Receptor, EphB4; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1