Elucidating the Role of Pyrophosphate Metabolism and ANKH, Key Factors in Regulation of Calcification in Health and Disease

Institution: The University of Oxford
Investigators: Dr Peter Cain, Dr Jim Dunford, Professor Paul Wordsworth, Professor Graham Russel, Professor Andrew Carr
Stream: Research Fellowship
Topic: Biology
Status: Live

Deposition of calcium containing crystals, known as calcium pyrophosphate dihydrate (CPPD), in joint cartilage (chondrocalcinosis) is a common but poorly understood cause of arthritis, particularly in the elderly. Chondrocalcinosis affects at least 20% of the population over 60 years of age. Although most cases occur out of the blue there are also families with clearly inherited forms of the condition that have been described, implying a significant genetic effect.

We have made key discoveries in the field of arthritis by being the first to characterize abnormalities in the ANKH protein, which transports pyrophosphate out of cells, as a cause of chondrocalcinosis. This work has led to instant international recognition and was selected as a highlighted plenary oral presentation at the American College of Rheumatology Annual Scientific Meeting.

We now intend to study the ways in which ANKH is expressed by cells, its function as a transporter of pyrophosphate, its interactions with other proteins and the ways in which specific disease associated ANKH variants alter these functions. The new knowledge that this creates will help us to understand the causes of chondrocalcinosis better and may identify ways in which the functions of ANKH could be modified to reduce the risk of this type of arthritis for which there is currently no specific effective treatment.

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