Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Osteoarthritis (OA) is characterized by progressive destruction of all joint tissues including inflammation of the synovial membrane. The histological changes that occur in OA present a range of abnormalities in the synovial membrane including fibrosis. Members of the ephrin family, the EphB4 receptor and its specific ligand ephrin-B2, were found to positively impact the abnormal structure and metabolism of OA subchondral bone and cartilage. In the context of evaluating the in vivo effect of the EphB4 receptor, we further investigated in vivo in mice the effect of bone-specific EphB4 overexpression (TgEphB4) on synovial membrane during OA.
Methods: Knee OA was surgically induced by the destabilization of the medial meniscus (DMM) in 10-week-old male EphB4 homozygous (TgEphB4) and wild-type (WT) mice. Synovial membrane evaluations were performed at 12 weeks post-surgery using histology, immunohistochemistry, and real-time PCR.
Results: Data demonstrated a significant decrease in the synovial membrane thickness (p≤0.02), pro-collagen type I (p≤0.01), and fibrin (p≤0.04) in DMM-TgEphB4 compared to DMM-WT. The expression of the fibrotic markers connective tissue growth factor (CTGF, p≤0.02), smooth muscle actine α (SMAα, p≤0.03) and serum cartilage oligomeric matrix protein (COMP, p≤0.03) were all significantly reduced in DMM-TgEphB4 compared to DMM-WT. Although the TGF-β was decreased in the DMM-TgEphB4 mice, the difference did not reach statistical significance. However, the synthesis of a member of the heat shock protein family (HSP), HSP90β, known to have a crucial role in enhancing TGF-β signaling, was significantly decreased (p≤0.03) in DMM-TgEphB4.
Conclusion: This is the first in vivo evidence showing that protecting the subchondral bone prophylactically reduces the severity of pathological changes in the synovial membrane during the OA process. This study thus stresses the in vivo importance of subchondral bone biology in OA tissues. It also provides evidence that changes in the synovial membrane are an integral part of the OA disease process. In addition, these data define the EphB4 receptor as a potential novel therapeutic avenue for the treatment of the disease.
Disclosure:
G. Valverde-Franco,
None;
D. Hum,
None;
B. Lussier,
None;
K. Matsuo,
None;
J. P. Pelletier,
None;
M. Kapoor,
None;
J. Martel-Pelletier,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-in-vivo-role-of-bone-specific-ephb4-receptor-overexpression-in-osteoarthritic-synovial-membrane/