Scottish Consortium TMaT Programme: 'Does mesenchymal stem cell-mediated synovial hyperplasia after traumatic joint surface injury affect the development of secondary osteoarthritis?' (360G-Wellcome-105424_Z_14_Z)

Apart from symptomatic relief through analgesics or joint replacement surgery no existing treatment prevents or reverses the development of osteoarthritis. Traumatic osteoarthritis is a result of injury to the joint from trauma or damage from abnormal joint biomechanics. We will investigate the role of the transcriptional co activator Yes-Associated Protein (YAP), a downstream target of the Hippo Pathway, in the post-traumatic synovial hyperplasia sustained by the proliferation of label-retaining mesenchymal stem cells (MSC) following traumatic joint injuries. We will correlate temporal expression patterns of YAP and MSC proliferation in tissues obtained from joint trauma patients and in a mouse model of traumatic joint injury with development of posttraumatic osteoarthritis. Using in vitro and in vivo knockdown experiments we will establish whether YAP is required for MSC proliferation and synovial hyperplasia. By creating mouse models that allow conditional knockout experiments of YAP and using the joint injury models of post-traumatic osteoarthritis we will establish whether inactivation of YAP following joint surface injury affects OA development. This would validate YAP preclinically as a potential drug target to prevent the development of post-traumatic OA.