Scientists identify new bone protecting protein

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 believe 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 one million of them requesting treatment. Osteoporosis affects around three 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, published in the Journal of Biological Chemistry, 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 utilised 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 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-6 could offer a completely new approach to treatment.”

The TSG-6 molecule is subject of a patent application filed by Isis Innovation, the technology transfer company for the University of Oxford.

For more information, a copy of the paper or to arrange an interview with Professor Tony Day or Dr Afsie Sabokbar, contact Media Relations Officers in Manchester and Oxford respectively, Mikaela Sitford on 0161 275 2111 or Mikaela.Sitford@manchester.ac.uk and Jonathan Wood on 01865 280530

jonathan.wood@admin.ox.ac.uk.

A copy of the paper ‘TSG-6 regulates bone remodelling through the inhibition of osteoblastogenesis and osteoclast activation’ by David J. Mahoney, Katalin Mikecz, Tariq Ali, Guillaume Mabilleau, Dafna Benayahu, Anna Plaas, Caroline M. Milner, Anthony J. Day and Afsaneh Sabokbar is also available at http://www.jbc.org/cgi/content/full/283/38/25952

The University of Manchester Faculty of Life Sciences, with more than 1,000 people involved in research, 1,700 undergraduate students and an annual total budget of £65 million, is one of the largest and most successful unified research and teaching organisations of its kind in Europe. See http://www.ls.manchester.ac.uk/

The Botnar Research Centre, housing the Oxford University Institute of Musculoskeletal Sciences, opened in 2002 to enable and encourage research and education into the causes of musculoskeletal diseases and their treatment. It provides a state-of-the-art facility on the Nuffield Orthopaedic Centre site for its research activities. See http://www.ndos.ox.ac.uk/

The Arthritis Research Campaign (arc) is the fourth largest medical research charity in the UK, raising more than £30m in 2006/7 entirely from public donations. It currently funds more than 350 research projects into all types of arthritis and musculoskeletal conditions in medical schools and hospitals around the UK, and also has an extensive educational remit. http://www.arc.org.uk

Isis Innovation is the University of Oxford’s technology transfer company. In the last financial year Isis concluded 74 licensing and option deals, arranged 102 consulting deals, providing access to Oxford experts, and filed 68 new patent applications. Isis also formed 4 new spin-out companies based on University inventions, bringing the total number of Oxford spin-outs to 67. Isis Enterprise, a division of Isis, also offers consulting expertise and advice in technology transfer and open innovation. See www.isis-innovation.com