Meet the teams: Bristol Bone Biologists

Understanding the onset and development of osteoarthritis

Osteoarthritis is the most common joint disease globally, with 8 million people suffering from this disease in the UK alone. Astronauts returning from space are also more at risk of developing osteoarthritis than the general population. Currently there is no cure: the only treatments available focus on pain relief and ultimately joint replacement. While we know that genetics and mechanical loading (through use of the joint) are the major risks for osteoarthritis we still don’t completely understand how either affects the cells of the joint in the early disease stages. Zebrafish develop rapidly, share most of their genes with people, and are translucent. This allows us to watch cells in the living fish organise to form the skeleton and test for changes in response to genes or loading.

This project will use hypergravity to increase loading on the developing skeleton. We will use normal fish and those carrying a mutation in a gene that causes severe early onset osteoarthritis in humans. We will model how the cells experience changes to loading using computer modelling, and by doing experiments on the fish we will test how exposure to hypergravity affects cartilage, bone and joint development. As well as looking at the shape of the skeleton, we will also look in detail at how the cells behave: how they make the matrix that gives the skeleton its properties; whether the cells divide, move or die and how this affects the whole structure.

By doing this we hope to see how very early changes to cells lead to longer term changes to the joint that cause the disease. It will also inform us whether the genes that lead to premature osteoarthritis do so by making the cells of the skeleton more sensitive to altered loading than those of people without these mutations. If so we may be able to identify new treatments that work well in different groups of people.