Cellular inflammation pattern in post-traumatic osteoarthritisIn-vivo evaluation of the impact of pro-inflammatory cells and their pattern of activation on phenotype-specific post-traumatic OA in mice

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Osteoarthritis (OA) is a common and painful disease gaining clinical relevance due to both the increasing mean age of the population of most countries in the world and the incidence of OA being higher in older age groups. It is believed that OA will become the 4th leading cause of disability worldwide by 2020. In particular the post-traumatic OA occurs after a joint injury and accounts for at least 12 % of all OA and up to 25% of OA in susceptible joints such as the knee. Not all injuries with apparently similar instability will go on to develop OA, and therefore defining “post-traumatic” and what factors drive the long-term OA-risk remains challenging. Furthermore even in the group of post-traumatic OA phenotype-specific differences occur. In particular synovitis and the overproduction of cytokines and growth factors can influence the production of degenerative enzymes that lead to the clinical syndrome of OA. Despite the advances in understanding the influence of the role of inflammation in the pathogenesis of OA, evidence regarding specific pathophysiological pathways in post-traumatic OA and if these differ from non-OA-inducing joint injury is scarce, and thus effective treatment options are missing.The aim of the proposed research project is to define the cellular inflammation pattern in the phenotype-specific post-traumatic osteoarthritis and how this may be influenced by specific joint injuries using an established animal model. This study will help to determine the interaction of the cellular response that causes OA and give further insight into the disturbed homeostasis of OA joints and provide further knowledge in the pathogenesis of this debilitating disease. In this study we will evaluate the cellular activation pathways of inflammatory cells, and the local, regional and systemic pattern of inflammatory/immune cell activation associated with post-traumatic OA. We will investigate the correlation between immune activation in different compartments with cartilage and bone pathology. Therefore in the future the findings of this study will help to investigate into early therapeutic intervention in the beginning of post-traumatic osteoarthritis and to prevent the proinflammatory cells that play a crucial role in the pathogenesis of OA from migrating into the joint at risk.