To examine the regulatory role of prolyl hydroxylases on hypoxia-induced inflammatory pathways and cartilage degradation in RA

Lead Researcher:

Dr Ursula Fearon

Award Date:

1 January 2013

Host Institution:

University College Dublin

Scheme:

Health Research Award

Summary:

Arthritis is a leading cause of disability that affects up to 15% of the population and is the most common cause of pain in our society especially in the elderly, a section of the population expanding rapidly in the next decade. 2% suffer from inflammatory arthritis (IA) such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). IA causes joint damage and disability and is associated with co-morbidities such as cardiovascular disease, malignancy and metabolic disorders. Current medicines don’t work for all patients or may cause infection, so new treatments are needed. The costs of inflammatory arthritis to both the individual and society are high, and include economic and social costs, drugs, hospitalisations, lost workdays, cost to family and carers and an overall reduced quality of life. In the joints of patients with IA many new blood vessels grow, allowing immune cells from the blood to invade into the joint, leading to low oxygen levels (hypoxia). We have previously shown that the joints of patients with IA are hypoxic, resulting in increased inflammation, leading to destruction of cartilage and bone. This ultimately results in functional disability. Furthermore we know that the level of hypoxia in the joint may alter patients response to current medicine. Specific substances called prolyl hydroxylases can regulate the level of hypoxia in the joint which may increase inflammatory pathways that are involved in eating away cartilage and bone. In this proposal we examine how these hydroxylases control oxygen metabolism and inflammation in the joint of patients with IA. Furthermore we will test in cells isolated from patients with IA if blocking these substances reduces inflammation, leading to development of new medicines for prevention and resolution of arthritis.