Integrins in osteoarthritis and cartilage repair

β-1整合素是软骨细胞-基质相互作用的重要受体，控制软骨组织的结构组织和生物力学特性，是维持正常关节软骨功能所必需的。我们已经部分阐明了β-1整合素在软骨细胞力学转导和骨关节炎发生中的作用，并提供了胶原结合的α-10-β-1整合素有助于软骨形态发生的证据，并且是骨髓间充质干细胞高效软骨形成所必需的。在本项目中，我们将进一步阐述胶原结合整合素在关节软骨功能、软骨细胞力学转导和黏附中的作用。我们的主要目标是剖析单个胶原相互作用的整合素在骨关节炎的发展中的作用，以及β1整合素对细胞因子和机械刺激的反应。因此，我们将利用在软骨细胞中缺乏β1整合素的小鼠，以及在不同的组合中，胶原结合的α1β1、α2β1和α10β1整合素异二聚体。我们还旨在进一步研究α10整合素基因的过表达对骨髓间充质干细胞和诱导的多能干细胞(IPSCs)的软骨形成和再生能力的影响。

β1 integrins are essential receptors for chondrocyte-matrix interactions controlling structural organization and biomechanical properties of cartilaginous tissues, which are required to maintain normal articular cartilage function. We have partially elucidated the role of β1 integrins for chondrocyte mechanotransduction and for the development of osteoarthritis, and provided evidence that the collagen-binding α10β1 integrin contributes to cartilage morphogenesis and is required for efficient chondrogenesis of MSCs. In this project, we will further elaborate the impact of collagen-binding integrins in articular cartilage function, chondrocyte mechanotransduction and adhesion using genetic, molecular, imaging and biomechanical tools. Our major goals are to dissect the contribution of individual collagen-interacting integrins to the development of osteoarthritis and to the response of β1 integrins to cytokine and mechanical stimulation. Therefore, we will utilize mice lacking β1 integrins specifically in chondrocytes and, in various combinations, the collagen-binding α1β1, α2β1 and α10β1 integrin heterodimers. We also aim to further investigate the effect of overexpression of the gene encoding α10 integrin (Itga10) on chondrogenic and regenerative potential of MSCs as well as induced pluripotent stem cells (IPSCs).