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Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes.
Arthritis Res Ther. 2009; 11(4):R119.AR

Abstract

INTRODUCTION

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+Show Affiliations

Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec, Canada. kwantats@yahoo.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19664212

Citation

Kwan Tat, Steeve, et al. "Treatment With Ephrin B2 Positively Impacts the Abnormal Metabolism of Human Osteoarthritic Chondrocytes." Arthritis Research & Therapy, vol. 11, no. 4, 2009, pp. R119.
Kwan Tat S, Pelletier JP, Amiable N, et al. Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes. Arthritis Res Ther. 2009;11(4):R119.
Kwan Tat, S., Pelletier, J. P., Amiable, N., Boileau, C., Lavigne, M., & Martel-Pelletier, J. (2009). Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes. Arthritis Research & Therapy, 11(4), R119. https://doi.org/10.1186/ar2782
Kwan Tat S, et al. Treatment With Ephrin B2 Positively Impacts the Abnormal Metabolism of Human Osteoarthritic Chondrocytes. Arthritis Res Ther. 2009;11(4):R119. PubMed PMID: 19664212.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment with ephrin B2 positively impacts the abnormal metabolism of human osteoarthritic chondrocytes. AU - Kwan Tat,Steeve, AU - Pelletier,Jean-Pierre, AU - Amiable,Nathalie, AU - Boileau,Christelle, AU - Lavigne,Martin, AU - Martel-Pelletier,Johanne, Y1 - 2009/08/07/ PY - 2009/03/17/received PY - 2009/07/06/revised PY - 2009/08/07/accepted PY - 2009/8/12/entrez PY - 2009/8/12/pubmed PY - 2009/12/17/medline SP - R119 EP - R119 JF - Arthritis research & therapy JO - Arthritis Res. Ther. VL - 11 IS - 4 N2 - INTRODUCTION: 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. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/19664212/Treatment_with_ephrin_B2_positively_impacts_the_abnormal_metabolism_of_human_osteoarthritic_chondrocytes_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar2782 DB - PRIME DP - Unbound Medicine ER -