How do circadian clocks in chondrocytes contribute to cartilage function in health and disease

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This research focuses on the molecular/cellular mechanisms of biological clocks in the joint cartilage and their contributions to the development and severity of damage in osteoarthritis (OA). Circadian (about a day) clocks are endogenous time pieces in our bodies that are responsible for generating 24 hour rhythms in behaviour and physiology. Disruptions of circadian rhythms by advanced age, shift work or jet lag can have severe impacts on body functions and disease risks. By culturing chondrocyte cells (the only cell type in cartilage) in petri dishes, isolating cartilage pieces, and a surgical operation which mimics OA in clock disrupted mouse knee joint, we expect to unravel: 1) Which rhythmic genes in cartilage rely on the local chondrocyte clock to maintain their circadian pattern of expression? 2) Can we target cartilage circadian clock proteins as a novel approach to alter chondrocyte gene expression? 3) Do alterations in specific components of the clock mechanism cause early onset OA, or leave mice more susceptible to surgical injury-induced OA? This project will generate new data and knowledge that will benefit researchers working on circadian biology, chondrocyte biology, ageing and joint diseases. It is also likely to benefit pharmaceutical industries who are interested in developing new approaches to targeting arthritic diseases. Outcomes will advance our understanding of the role circadian rhythms play in the healthy state of the joint cartilage, so will also be of value to the general public.