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

骨关节炎是一种退行性关节疾病，是英国致残的主要原因。在英国大约有850万人患有中度到重度OA。这些患者主要年龄在45岁以上，该病往往成为60岁以上患者的重大负担。目前缺乏治疗骨关节炎的有效药物，而且用于缓解疼痛的药物往往是不够的。关节置换术是晚期骨性关节炎患者唯一的治疗方法，2011年英国有66436例髋关节置换术和77578例膝关节置换术。鉴于目前人口老龄化的趋势，骨关节炎，年龄是一个重要的危险因素，将成为一个日益严重的社会问题，预计到2030年将有1700万OA患者。减缓或阻止疾病进展的能力将显著改善生活质量和骨关节炎的经济负担。尽管经过多年的研究，还没有药物可以减缓或阻止骨关节炎的发展。在某种程度上，这是因为用于任何不危及生命的疾病的药物必须非常安全。进行骨关节炎临床试验的费用令人望而却步。有必要开发新的策略来对抗骨关节炎。饮食与骨关节炎之间的关系已经在一定程度上得到了探讨。在大型人群研究中，一些食物的高摄入量与疾病进展缓慢有关，这些研究表明饮食可以影响关节健康。然而，我们需要更多地了解饮食中的化合物是如何起作用的，什么是最理想的食物，吃多少，用什么组合。当我们知道了这一点，我们就可以仔细地设计受控的人体研究，提供明确的数据，为公众提供最佳的饮食策略，以预防和延缓骨关节炎的进展。食品中有许多具有生物活性的化合物。到目前为止，我们关注的是萝卜硫素，西兰花和相关蔬菜中含有大量的萝卜硫素。在实验室模型中，萝卜硫素可以防止软骨破坏，我们已经在骨关节炎小鼠模型中证实了这种能力。我们已经确定了萝卜硫素在人体软骨细胞中起作用的主要途径。我们还从饮食中发现了一些其他化合物，在实验室分析中具有活性。目前的应用是了解每种饮食衍生化合物保护软骨的机制。然后，我们将用它来测试活性化合物的混合物，以确定可以保护软骨、减缓或预防骨关节炎的最佳组合。然后我们将测试它对人类骨关节炎关节的影响。当我们整理和分析了所有这些数据后，我们将设计一项试验，研究在饮食中提供这种化合物组合的最佳方式，以保护关节免受骨关节炎的侵害。

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.