Candela Maria Elena, Wang Chao, Gunawardena Aruni T, Zhang Kairui, Cantley Leslie, Yasuhara Rika, Usami Yu, Francois Noelle, Iwamoto Masahiro, van der Flier Arjan, Zhang Yejia, Qin Ling, Han Lin, Enomoto-Iwamoto Motomi
Department of Surgery, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
School of Biomedical Engineering Science, and Health Systems, Drexel University, Philadelphia, PA, United States of America.
PLoS One. 2016 Jun 9;11(6):e0156783. doi: 10.1371/journal.pone.0156783. eCollection 2016.
Osteoarthritis (OA) is one of most common skeletal disorders and can affect synovial joints such as knee and ankle joints. α5 integrin, a major fibronectin receptor, is expressed in articular cartilage and has been demonstrated to play roles in synovial joint development and in the regulation of chondrocyte survival and matrix degradation in articular cartilage. We hypothesized that α5 integrin signaling is involved in pathogenesis of OA. To test this, we generated compound mice that conditionally ablate α5 integrin in the synovial joints using the Gdf5Cre system. The compound mice were born normally and had an overall appearance similar to the control mice. However, when the mutant mice received the OA surgery, they showed stronger resistance to osteoarthritic changes than the control. Specifically the mutant knee joints presented lower levels of cartilage matrix and structure loss and synovial changes and showed stronger biomechanical properties than the control knee joints. These findings indicate that α5 integrin may not be essential for synovial joint development but play a causative role in induction of osteoarthritic changes.
骨关节炎（OA）是最常见的骨骼疾病之一，可影响膝关节和踝关节等滑膜关节。α5整合素是一种主要的纤连蛋白受体，在关节软骨中表达，并已被证明在滑膜关节发育以及关节软骨中软骨细胞存活和基质降解的调节中发挥作用。我们假设α5整合素信号传导参与骨关节炎的发病机制。为了验证这一点，我们使用Gdf5Cre系统生成了在滑膜关节中条件性敲除α5整合素的复合小鼠。这些复合小鼠正常出生，整体外观与对照小鼠相似。然而，当突变小鼠接受骨关节炎手术时，它们对骨关节炎变化的抵抗力比对照更强。具体而言，突变膝关节的软骨基质水平和结构损失以及滑膜变化较低，并且比对照膝关节表现出更强的生物力学特性。这些发现表明，α5整合素可能对滑膜关节发育不是必需的，但在骨关节炎变化的诱导中起因果作用。
