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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

创伤后骨关节炎的细胞炎症模式体内评估促炎细胞的影响及其激活模式对小鼠表型特异性创伤后骨关节炎的影响

基本信息

批准号：
395752904
负责人：
Dr. Patrick Haubruck
金额：
--
依托单位：
Raymond Purves Bone and Joint Research Laboratory
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2018
资助国家：
德国
起止时间：
2017-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/395752904?language=en
关键词：
Cellular inflammation pattern post traumatic

项目摘要

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.

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人口的平均年龄增加以及OA在老年组中的发病率较高，因此获得了临床意义。据信，到2020年，OA将成为全球第四大残疾原因。特别是创伤后OA发生在关节损伤后，占所有OA的至少12%，在易感关节如膝关节中占OA的高达25%。并非所有具有明显相似不稳定性的伤害都会继续发展为OA，因此定义“创伤后”以及哪些因素导致长期OA风险仍然具有挑战性。此外，即使在创伤后OA组中，也存在表型特异性差异。特别是滑膜炎和细胞因子和生长因子的过度产生可以影响导致OA临床综合征的退行性酶的产生。尽管在理解炎症在OA发病机制中的作用的影响方面取得了进展，但关于创伤后OA的特定病理生理学途径的证据以及这些途径是否与非OA诱导的关节损伤不同的证据很少，因此，缺乏有效的治疗选择。拟议的研究项目的目的是确定表型特异性后-创伤性骨关节炎以及使用已建立的动物模型如何受到特定关节损伤的影响。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关节的稳态紊乱，并提供进一步的知识，这种衰弱性疾病的发病机制。在这项研究中，我们将评估炎症细胞的细胞活化途径，以及与创伤后OA相关的局部，区域和全身炎症/免疫细胞活化模式。我们将研究不同区室中的免疫激活与软骨和骨病理之间的相关性。因此，在未来，这项研究的结果将有助于探讨创伤后骨关节炎开始时的早期治疗干预，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。