The role of purinergic signalling in cartilage and joint health

三磷酸腺苷在细胞内能量代谢中的作用是众所周知的，但三磷酸腺苷和一些相关的核苷酸也是重要的胞外信号分子。这种所谓的嘌呤能信号是通过一些细胞表面受体介导的，这些受体分为四个P1受体和十五个P2受体。针对特定受体的药物已经在许多疾病中临床使用。有很好的证据表明，嘌呤能信号参与肌肉骨骼系统的动态平衡，包括软骨，这是关节健康的关键组织。然而，关于这个信号系统在软骨中的作用的具体细节仍然不清楚。该项目将表征不同年龄的人和小鼠软骨中嘌呤能信号成分的表达，并测量与软骨发育和分解代谢相关的变化。然后，它将测试软骨生理学中关键的P1或P2受体的功能。该项目将使用体外和体内模型，涉及多种细胞和分子生物学和生理学技术。

ATP is well known for its role in intracellular energy metabolism but ATP and a number of related nucleotides are also important extracellular signalling molecules. This so-called purinergic signalling is mediated via a number of cell surface receptors grouped into four P1 receptors and fifteen P2 receptors. Drugs targeting specific receptors are already in clinical use in a number of diseases. There is good evidence that purinergic signalling is involved in the homeostasis of the musculoskeletal system, including cartilage, a tissue key to joint health. However, specific details about the role of this signaling system in cartilage remain poorly defined.The project will characterise the expression of the components of purinergic signalling in cartilage, both mouse and human, across age and measure changes associated with cartilage development and catabolism. It will then assay function of key P1 or P2 receptors in cartilage physiology. The project will involve several techniques of cell and molecular biology and physiology, using both in vitro and in vivo models.