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

骨关节炎（OA）是一种常见的疼痛性疾病，由于世界上大多数国家的人口平均年龄不断增加，并且OA在老年群体中的发病率较高，因此具有临床相关性。据信，到2020年，OA将成为全球第四大致残原因。特别是创伤后骨性关节炎发生在关节损伤之后，至少占所有骨性关节炎的12%，在易感关节（如膝关节）中高达25%。并非所有具有类似不稳定性的损伤都会发展为骨关节炎，因此定义“创伤后”以及导致长期骨关节炎风险的因素仍然具有挑战性。此外，即使在创伤后OA组中，表型特异性差异也会发生。特别是滑膜炎和细胞因子和生长因子的过量产生会影响导致骨性关节炎临床综合征的退行性酶的产生。尽管在了解炎症在骨性关节炎发病机制中的作用方面取得了进展，但关于创伤后骨性关节炎的具体病理生理途径以及这些途径与非骨性关节炎诱导的关节损伤是否不同的证据很少，因此缺乏有效的治疗方案。拟建研究项目的目的是利用已建立的动物模型，确定表现型特异性创伤后骨关节炎的细胞炎症模式，以及特异性关节损伤如何影响细胞炎症模式。这项研究将有助于确定导致OA的细胞反应的相互作用，并进一步了解OA关节的体内平衡紊乱，并为这种使人衰弱的疾病的发病机制提供进一步的知识。在这项研究中，我们将评估炎症细胞的细胞激活途径，以及与创伤后OA相关的局部、区域和全身炎症/免疫细胞激活模式。我们将研究不同区室的免疫激活与软骨和骨病理之间的关系。因此，在未来，本研究的发现将有助于研究创伤后骨关节炎早期的治疗干预，并防止在OA发病机制中起关键作用的促炎细胞迁移到危险的关节。

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.