29 Sep 08

Dr Afsie Sabokbar, from the Nuffield Department of Orthopaedic Surgery, led the research team at Oxford University. They are now investigating how the protein may be used as an effective therapy.

Researchers at the Universities of Oxford and Manchester have identified a naturally occurring protein molecule that could help develop new therapies for conditions such as osteoporosis and osteoarthritis.

The protein, called TSG-6, not only protects against inflammation but also actively inhibits bone erosion in those affected by disease. The findings, published in the Journal of Biological Chemistry, advance our understanding of tissue regeneration and repair.

Inflammation is the body’s natural response to tissue injury, but if it works overtime, the effects can be devastating. When the inflammatory response goes awry tissue is destroyed faster than it can be replaced and, in the joints, this means deterioration of cartilage and bone.

Osteoarthritis is the most common form of arthritis affecting around 8 million people in the UK, with 1 million of them requesting treatment. Osteoporosis affects around 3 million people in the UK, and more than 230,000 fractures occur per year due to the disease.

The protein TSG-6 is produced at high levels in inflamed tissue such as the joints of arthritis patients and the lungs of asthmatics. TSG-6 has previously been shown to protect against inflammation and cartilage destruction. The new research, funded by the Arthritis Research Campaign, indicates that it can also actively inhibit bone erosion where necessary.

Dr Afsie Sabokbar from the Nuffield Department of Orthopaedic Surgery at Oxford University and Professor Tony Day of the University of Manchester's Faculty of Life Sciences have investigated the effects of TSG-6 on bone cells.

'Bone formation and bone breakdown are happening all the time and we now have good evidence that TSG-6 normally works to maintain a balance between these two processes,’ said Dr Sabokbar.

'Our latest research, using cells grown in culture, shows that in inflammatory conditions, TSG-6 can inhibit the erosion of bone. This suggests that it might halt the excessive erosion that occurs in conditions such as arthritis and osteoporosis.’

The teams in Oxford and Manchester are now investigating the molecular basis of TSG-6 function to evaluate how it may be used as an effective therapy. Unlike some therapies, TSG-6 does not appear to interfere with other anti-inflammatory mechanisms or normal cell processes. This means that it could be used therapeutically without affecting the body’s ability to fight infection.

Professor Day added: ‘To have a naturally occurring substance that can effectively inhibit bone erosion would be a major breakthrough. We are now scaling up production of TSG-6 for further studies with the aim of producing an optimised form of this protein that can form the basis of pre-clinical and hopefully, in the longer term, clinical trials.’

Medical director of the Arthritis Research Campaign Professor Alan Silman said: ‘Osteoarthritis is the most important cause of joint damage in the elderly. Although the manifestation of the disease results from chronic damage to the cartilage and the underlying bone in the joints, there is still a need to identify the underlying chemical processes that lead to these tissue changes despite several years of research.’

‘Research such as this importantly has focussed on the normal processes that protect the bones against inflammation. Thus the work on this naturally occurring protective protein is a major step forward, and increasing the level or activity of TSG could offer a completely new approach to treatment.’