Researchers at the Universities of Manchester and Oxford have identified a naturally occurring protein molecule that not only protects against inflammation but also actively inhibits bone erosion in those affected by disease. The team believes their work could help develop new, possibly safer therapies for conditions such as osteoporosis and osteoarthritis.
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, with more than 230,000 fractures per year occurring due to osteoporosis.
The findings of this Arthritis Research Campaign-funded study represent a major advance in the understanding of tissue regeneration and repair.
The protein, called 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 been shown previously to protect against inflammation and cartilage destruction, but this recent research indicates that it can also actively inhibit bone erosion where necessary.
Professor Tony Day from the University of Manchester's Faculty of Life Sciences and Dr. Afsie Sabokbar from Nuffield Department of Orthopaedic Surgery, Botnar Research Centre, University of Oxford, have been investigating 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 utilized 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 or react normally.
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 optimized 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, Profesor 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 focused 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-6 could offer a completely new approach to treatment.”
Illustration: Microsoft clipart.
The University of Manchester News Item (09/29/08)
Arthritis Research Campaign Press Release (09/29/08)
Daily Record (09/29/08)
Abstract (Journal of Biological Chemistry, Vol. 283, Issue 38, 25952-25962, September 19, 2008)