Modulation of the Wnt signalling in the articular cartilage: is it all about the dose?

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This project aims to investigate key mechanisms maintaining the health of the articular cartilage, the tissue covering the edges of the long bones in the joint, allowing a smooth sliding of the bones while we move. The articular cartilage is affected by severe structural damage during the development of a disease called osteoarthritis. Osteoarthritis affects millions of people worldwide. People affected suffer chronic pain and disability with a severe decrease in the quality of life. The only available treatment is pain relief until cartilage damage is so severe that surgery is required. Surgery usually consists of surgical removal of the joint and its replacement with a prosthetic. By understanding the mechanisms keeping the cartilage healthy, we could design new drugs to re-establish the cartilage in cases where it is lost or damaged.We already have evidence showing that a class of proteins called Wnts (pronounced Wenz) are important to maintain cartilage integrity. Thus, the final goal of this application is to understand how these Wnts work. We have three aims: 1) to clarify which other proteins might work with the Wnts within a group of receptors, called frizzled receptors, which are present on cartilage cells; 2) to identify whether very small molecules called microRNAs can modify the function of the Wnts from within the cell; 3) determine whether the function of the Wnts is altered during OA development and whether re-establishing their original activity could be exploited in the future via development of a drug as a therapeutic treatment.