Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes.
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.
Kwan Tat
Steeve
S
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec, Canada. kwantats@yahoo.fr
Pelletier
Jean-Pierre
JP
Amiable
Nathalie
N
Boileau
Christelle
C
Lavigne
Martin
M
Martel-Pelletier
Johanne
J
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
D036388:Ephrin-B2; D053583:Interleukin-1beta; D015850:Interleukin-6; D036224:Receptor, EphB4; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1