التفاصيل البيبلوغرافية
| العنوان: |
Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts |
| المؤلفون: |
Kwan Tat, Steeve, Pelletier, Jean‐Pierre, Amiable, Nathalie, Boileau, Christelle, Lajeunesse, Daniel, Duval, Nicolas, Martel‐Pelletier, Johanne |
| المصدر: |
Arthritis & Rheumatism ; volume 58, issue 12, page 3820-3830 ; ISSN 0004-3591 1529-0131 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2008 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Objective Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts. Methods The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme‐linked immunosorbent assay. Results EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H‐OA osteoblasts, EphB4 receptor expression levels were significantly increased in L‐OA osteoblasts, with no difference between normal and H‐OA osteoblasts. EphB4 receptor levels in L‐OA osteoblasts were significantly up‐regulated by prostaglandin E 2 (PGE 2 ) and interleukin‐17 (IL‐17). Ephrin B2, PGE 2 , and IL‐17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL‐1β, IL‐6, matrix metalloproteinase 1 (MMP‐1), MMP‐9, MMP‐13, and RANKL, but not MMP‐2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3‐kinase/Akt pathway. Conclusion This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/art.24029 |
| الإتاحة: |
https://doi.org/10.1002/art.24029Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.D11D8308 |
| قاعدة البيانات: |
BASE |
