Synergistic combinations of diet-derived bioactives to maintain joint health and prevent osteoarthritis

点击翻译按钮获取中文摘要

Osteoarthritis is a degenerative joint disease which is a leading cause of disability in the UK. Approximately 8.5 million people in the UK suffer from moderate to severe OA. These patients are predominantly older than 45 years of age, with the disease often becoming a significant burden in patients over 60 years of age . There is a lack of effective drugs available to treat osteoarthritis and the drugs given for pain relief are often not sufficient . Joint replacement is the only treatment offered to patients at later stages of the disease with 66,436 hip and 77,578 knee replacements due to OA performed in the UK in 2011. Given the current trend toward an older population, osteoarthritis, for which age is an important risk factor, will be an increasing problem for society with 17 million OA patients predicted for 2030 . The ability to slow or stop progression of the disease would significantly improve both quality of life and the economic burden of osteoarthritis. Despite many years of research, there are no drugs to slow or stop the progression of osteoarthritis. In part, this is because drugs for use in any disease which is not life threatening must be very safe. The costs of running clinical trials in osteoarthritis are prohibitive. There is a need to develop new strategies to combat osteoarthritis.The connection between diet and osteoarthritis has been explored to some extent. High intake of some foodstuffs has been linked to slower progression of the disease in large population-based studies and these show that diet can influence joint health. However, we need to know much more about how compounds found in the diet work, what are the optimal foods to eat, in what amount and in what combination. When we know this, we can then carefully design controlled human studies to provide clear data from which to advise the public on optimal dietary strategies to both prevent and delay the progression of osteoarthritis. There are many compounds in food with biological activities. To date, we have focused on sulforaphane, found at high amounts in broccoli and related vegetables. Sulforaphane can prevent cartilage destruction in laboratory models and we have confirmed this ability in a mouse model of osteoarthritis. We have identified the main pathway by which sulforaphane acts in human cartilage cells. We have also identified a number of other compounds, derived from the diet, which have activity in the laboratory assays.The current application is to gain knowledge of the mechanism(s) by which each diet-derived compound acts to protect cartilage. We will then use this to test mixtures of active compounds to identify the best combination which can protect cartilage and slow or prevent osteoarthritis. We will then test this for its impact upon the human osteoarthritic joint.When we have collated and analysed all these data, we will then design a trial to investigate the best way to deliver this combination of compounds in the diet in order to protect the joint from osteoarthritis.