BioGrOA: Imaging joint biomechanics in growth and osteoarthritis

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、举起和跳跃时施加在它们身上的各种通常是巨大的负荷。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。患骨关节炎的关节，最常见的是膝盖和臀部，会经历结构恶化，其特征是覆盖骨骼的关节软骨的丧失，而关节软骨通常可以进行无痛的关节运动。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。这一建议将通过确定骨骼在儿童和青少年时期的生长方式，改变关节结构如何适应施加在它们身上的巨大负荷来改变这一现状。我们的研究团队开发了新的成像技术来解决这个问题。利用这项技术，我们现在可以对老鼠的膝关节进行成像，就像我们在日常生活中看到的那样。我们可以看到关节的软骨和骨头如何对这些负荷做出反应，最重要的是，它们如何改变自己的结构来应对这种情况。因此，我们将把这项技术应用于老鼠的膝关节，我们知道老鼠的膝关节在早期生长得很快，随着年龄的增长会患上骨关节炎。我们还将检查一大批人类患者，看看他们的关节是否随着童年和青春期的成长而改变了形状。这项研究将确定是否有特定的关节结构随着负荷和衰老而变化，因此将为谁可能患上骨关节炎提供线索。此外，它将确定儿童和青少年时期的身高是否会使人易患与骨关节炎相关的关节变化。总之，这将使我们能够更好地识别那些有骨关节炎风险的人，因此将对患者有巨大的好处。如果我们要减轻这种疾病的医疗和经济负担，这一点至关重要。

Throughout life, our joints change continuously and adapt to the varying and often huge loads 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. Osteoarthritic joints, most often knees and hips, undergo structural deterioration, characterised by loss of the joint cartilage which covers the bone and normally allows pain-free joint movement. 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. This proposal will change this by identifying whether the way in which the skeleton grows during childhood and adolescence, changes how joint structures adapt to the huge loads placed upon them.Our research team has developed new imaging technologies to enable us to address this. Using this technology, we are now able to image mouse knee joints whilst they are experiencing loading, like that is seen in our everyday life. We are able to see how the cartilage and the bones of the joint react to these loads, and most importantly, how they change their structure in response to this. Therefore, we will apply this technology to mouse knee joints which we know grow very quickly in early life, and which develop osteoarthritis with ageing. We will also examine a large cohort of human patients to see if their joints have changed their shape in response to their childhood and adolescence growth. This research will identify if there are specific joint structures which change with loading and ageing, and therefore will offer clues into who may develop osteoarthritis. Further, it will identify if height during childhood and adolescence can predispose someone to joint changes linked to osteoarthritis. Together, this will allow us to better identify those at risk of osteoarthritis and therefore will have huge patient benefit. This is vital if we are to reduce the healthcare and economic burden of this disease.