Matrix fragments damage cartilage and cause osteoarthritis

Conditions such as osteoarthritis cause the destruction and loss of the cartilage tissue which lines the joints such as the knee and hip. Cartilage loss can be affected by a number of stimuli applied to articular cartilage. For example, the destructive molecules, known as the fibronectin fragments are formed from the breakdown of the extracellular matrix components and could increase cartilage loss. By contrast, loading the tissue during normal joint activity may help to prevent tissue destruction. Both types of stimuli influence the release of factors such as nitric oxide and the matrix metalloproteinases. These molecules, which are produced by the cartilage cells, can control the extent of cartilage loss. The way in which fibronectin fragments and mechanical load affect the release of nitric oxide and matrix metalloproteinases from cartilage cells is poorly understood. The pathways activated by the fibronectin fragments and mechanical load are likely to interact with each other. The project team (Reshma Tilwani) aims to find out how mechanical loading of cartilage can act to prevent tissue breakdown by blocking the destructive fibronectin fragment pathways. An understanding of these pathways will help to provide a focus for the development of safe targets for pharmacological and biophysical therapies for the treatment of osteoarthritis and provide new information for the development of tissue engineered implants.