Osteoarthritis: Going back to basics

当你站起来的时候，你是否经历过关节疼痛？或者休息一段时间后僵硬？在我们的一生中，我们的关节不断变化，以适应我们走路、跑步、举起和跳跃时对它们施加的各种各样的、往往是巨大的要求。然而，随着年龄的增长，我们的关节会发生结构变化，这可能会导致疼痛和僵硬，这通常与衰老有关。骨关节炎是最重要的与衰老相关的疾病，影响着英国近900万人。据估计，超过33%的45岁以上的英国人寻求治疗骨关节炎。因此，骨关节炎是一个主要的经济、社会和医疗负担。目前的骨关节炎治疗是有限的，主要包括使用止痛药和物理治疗。在一些个体中，骨关节炎进展到需要全关节置换的程度。目前我们还不能确定那些有患骨关节炎风险的人。我们也无法治疗那些处于疾病早期阶段的患者。为了改变这种状况，我们必须确定导致骨关节炎的基因、分子和过程。骨性关节炎的关节，最常见的是膝盖和臀部，经历结构恶化，其特征是覆盖骨末端的关节软骨的丧失，通常可以进行无痛的关节运动。在关节软骨中，常驻细胞类型——软骨细胞——需要保持一个非常稳定的“永久”状态，以便在整个生命中保存和保护这个组织。这与人体中另一种主要的软骨（生长软骨）形成了鲜明的对比，生长软骨负责所有骨骼的生长，奇怪的是，它与关节软骨有着几乎相反的特征。在生长软骨中，软骨细胞能够很容易地在不同的状态之间转换，从而使骨骼生长，因此只有一个“临时”状态。我之前已经证明，在骨关节炎中，关节软骨的“永久性”软骨细胞会转变为“临时”状态，就像在生长软骨中看到的那样。这个项目将研究为什么两种不同类型的软骨细胞（“永久性”和“永久性”）之间的转换。（暂时的）在关节软骨中产生不稳定的组织，容易恶化和骨关节炎。它还将研究我们是否可以通过生长软骨的任何异常来预测那些有患骨关节炎风险的人。总之，这项研究将确定明确的目标，然后可以在未来为患者的利益进行调查。如果我们要减少这种疾病的经济和社会影响，这一点至关重要。

Have you ever experienced an aching pain in your joints when you stand up? Or stiffness after periods of rest? Throughout life, our joints change continuously and adapt to the varying and often huge demands placed upon them as we walk, run, lift and jump. However, as we get older our joints undergo structural changes that may lead to the aching and stiffness that is often associated with ageing.Osteoarthritis is the most important ageing-related disease affecting almost 9 million people in the UK. It is estimated that more than 33% of the UK population aged over 45 have sought treatment for osteoarthritis. For this reason, osteoarthritis is a major financial, social and healthcare burden. Current osteoarthritis treatments are limited and largely consist of the use of pain-killers and physiotherapy. In some individuals, osteoarthritis progresses to the extent that total joint replacement is required. Currently we are unable to identify those at risk of developing osteoarthritis. We are also unable to treat those at early disease stages. To change this, we must identify the genes, molecules and processes which cause osteoarthritis. Osteoarthritic joints, most often knees and hips, undergo structural deterioration, characterised by loss of the joint cartilage which covers the bone ends and normally allows pain-free joint movement. In joint cartilage, the resident cell type - the chondrocyte - needs to maintain a very stable, 'permanent' state so as to preserve and protect this tissue throughout life. This is in stark contrast to the other main type of cartilage in the body (the growth cartilage), which is responsible for all bone growth and which strangely has almost opposite characteristics to the joint cartilage. In the growth cartilage, the chondrocytes are able to easily transition between different states to enable bone growth and therefore only ever have a 'temporary' state. I have previously shown that in osteoarthritis, the 'permanent' chondrocytes of the joint cartilage undergo a switch to a 'temporary' state, much like that seen in the growth cartilage. This project will examine why the switching between the two distinct types of chondrocytes ('permanent' vs. 'temporary') in the joint cartilage produces an unstable tissue prone to deterioration and osteoarthritis. It will also look to examine whether we can predict those at risk of osteoarthritis from any abnormalities in their growth cartilage. Together, this research will identify clear targets which could then in the future be investigated for patient benefit. This is vital if we are to reduce the economic and social impact of this disease.