The role of purinergic signalling in cartilage and joint health

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.