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Professor Philippa Hulley and Doctor Helen Knowles have been awarded funding by The Paget’s Association for their research on bone cells.

Philippa Hulley and Helen Knowles

Paget’s disease affects all three specialist bone cells that work together to engineer the mechanical architecture of human bones. These cell types are osteoblasts that build bone, osteoclasts that break it down and osteocytes that form a long-lived residential network, locally co-ordinating the work of the other two cells. Paget’s causes focal loss of bone where the osteoclasts become aggressively active and erode bone excessively and the osteoblasts fail to repair these weakened patches properly. This suggests a focal loss of control that is likely to come from the osteocytes because they live the longest of all the bone cells and provide a locally co-ordinated response to damage or changes in loading. The most common disease-causing mutation in Paget’s disease is in a gene called SQSTM1 and the research aims to investigate, for the first time, how this mutation affects the regulatory/ co-ordinating role of the osteocytes. 

Osteocytes are notoriously difficult to grow in the lab and, since Paget’s is a human disease, mouse models are limited in predicting mechanisms and responses to treatment. However, the researchers recently discovered how to make human osteocytes from donated bone tissue, scraps of “sawdust” leftover from cutting or drilling when knees and hips are replaced. The bone cells can be grown over several months in statically loaded, 3D mini-bone constructs that move through the adult bone formation process until mature osteocytes emerge. Using this technique, for the first time, we can investigate the effect of Paget’s mutations in human osteocytes and discover what these master cells do in Paget’s disease. 

On hearing the news Professor Hulley said, “Thank you!! This is very good news. It means a great deal to us to be able to develop our system in this way to be more helpful to patients. We are enormously grateful to the Paget’s Association for their interest and vision!” 

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