Integrins in osteoarthritis and cartilage repair

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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).