Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Activation of the EphB4 Receptor by Its Specific Ligand Ephrin B2 Positively Impacts Human Osteoarthritic Chondrocytes
Tat1, Steeve Kwan, Pelletier1, Jean-Pierre, Amiable1, Nathalie, Boileau1, Christelle, Lavigne2, Martin, Martel-Pelletier1, Johanne
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, QC
Department of Orthopaedic Surgery, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
We recently showed that treatment of human osteoarthritic (OA) subchondral bone osteoblasts by a member of the ephrin system, ephrin B2, inhibits the abnormal resorptive properties of these cells. Hence, we further investigated the possible implication of this ephrin and activation of its specific receptor EphB4 on the catabolic/anabolic activities of human OA chondrocytes.
Ephrin B2 and EphB4 receptor levels were determined by quantitative PCR and immunohistochemistry, and the effects of ephrin B2 by the expression/production of factors involved in the OA process. siRNA was used to investigate the ephrin B2 activation of EphB4 receptors.
Ephrin B2 and EphB4 receptors are expressed and produced by human normal and OA chondrocytes. Ephrin B2 protein levels were similar 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 IL-1b, IL-6, MMP-1, MMP-9, MMP-13, and PAR-2 expression levels, whereas MMP-2 was unaffected, and significantly increased collagen type II. It also markedly inhibited the IL-1b stimulated protein production of IL-6, MMP-1 and MMP-13. Moreover, data revealed that silencing the EphB4 receptor gene abolished the effects of ephrin B2, confirming that these effects are mediated by EphB4 receptors.
Our study is the first to provide data on the presence and role of ephrin B2/EphB4 receptors in human chondrocytes/cartilage. Activation of the EphB4 receptor by ephrin B2 positively impacts the abnormal metabolism of OA cartilage by inhibiting important catabolic factors involved in this disease while increasing anabolic activity.
To cite this abstract, please use the following information:
Tat, Steeve Kwan, Pelletier, Jean-Pierre, Amiable, Nathalie, Boileau, Christelle, Lavigne, Martin, Martel-Pelletier, Johanne; Activation of the EphB4 Receptor by Its Specific Ligand Ephrin B2 Positively Impacts Human Osteoarthritic Chondrocytes [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1287