The role of repellent factors in the maintenance of joint compartment border integrity

驱避因子在维持关节间室边界完整性中的作用

• 批准号: 163602671
• 负责人: Professorin Dr. Anja-Katrin Bosserhoff
• 金额: --
• 依托单位: Lehrstuhl für Biochemie und Molekulare Medizin
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/163602671?language=en
• 关键词: role; repellent; factors; maintenance; joint

The mechanical functions of joints depend on strict separation of the compartment borders. Crossing of the joint compartment boundaries and destruction of the cartilage compartment is found in inflammatory and degenerative joint diseases such as rheumatoid arthritis and osteoarthritis. We hypothesize that there are molecular cues at the joint compartment borders maintaining the integrity of these borders. Candidate molecules for this function are repellent factors, which are expressed in fetal and adult synovial tissue and cartilage. The principal purpose of the first grant period was to single out candidate repellent factors that may exert the function of establishing and maintaining tissue boundaries by the use of expression studies and functional studies. The cell types under scrutiny were synovial fibroblasts as potential invaders and chondrocytes as cells that may exert repellent activities. Their potential to produce repellent factors and react to repellent factors was studied in vitro in different model systems (migration, cartilage destruction, angiogenesis, proliferation etc.). We found primarily two candidate repellent factor families during the progress of the first period: the Robo/Slit- and the Netrin/UNC/DCC system. Both systems had strong impact on synovial and chondrocytic function. In the second period we aim to understand the molecular mechanisms behind the functional changes. Further, we focus on a way to influence the system looking for potential therapeutic or prognostic implication.

关节的机械功能依赖于隔间边界的严格分隔。炎性和退行性关节疾病，如类风湿性关节炎和骨性关节炎，可发现关节间隙边界的交叉和软骨间隙的破坏。我们假设在联合间隔边界处存在分子线索，以维持这些边界的完整性。这一功能的候选分子是排斥因子，它们在胎儿和成人的滑膜组织和软骨中表达。第一个授权期的主要目的是通过表达研究和功能研究挑选出可能发挥建立和维持组织边界功能的候选排斥因子。被仔细观察的细胞类型是作为潜在侵袭者的滑膜成纤维细胞和作为可能发挥排斥活性的软骨细胞。在不同的模型系统(迁移、软骨破坏、血管生成、增殖等)下，体外研究了它们产生排斥因子和对排斥因子的反应的能力。在第一阶段的进展过程中，我们主要发现了两个候选排斥因子家族：Robo/Sit-和Netrin/UNC/DCC系统。这两种系统对滑膜和软骨细胞功能都有很大影响。在第二阶段，我们的目标是了解这些功能变化背后的分子机制。此外，我们专注于一种影响系统的方法，以寻找潜在的治疗或预后意义。