Molecular mechanisms of cartilage degeneration in osteoarthritis

骨关节炎软骨退变的分子机制

• 批准号: nhmrc : 384414
• 负责人: Prof Amanda Fosang
• 金额: $ 30.51万
• 依托单位: Murdoch Childrens Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-mechanisms-cartilage-degeneration-osteoarthritis/95456
• 关键词: Molecular; mechanisms; cartilage; degeneration; osteoarthritis

Arthritis affects 15% of the entire Australian population and 50% in people over 60. The most common form of joint disease by far is osteoarthritis (OA). One of the central features of OA is the breakdown of the cartilage that covers the ends of bones in joints, and this is a major determinant of the long term outcome and need for joint replacement surgery. There are no current therapies that halt or reverse cartilage breakdown in OA. This is largely due to our incomplete understanding of the molecular changes and pathways involved in both the onset and progression of cartilage breakdown. Powerful new genomic approaches allow simultaneous screening of changes in a broad profile of genes, particulalrly in humans and mice following complete sequencing of their genomes. By applying this new technology in the earliest stages of cartilage degeneration in OA, the role of novel genes and the pathways involved in the onset of this disease process can be discovered. However, to investigate changes at the initiation of disease, tissue from animal rather than human joints must be used due to the difficulty in obtaining pre-symptomatic human cartilage. In order to maximise the number of genes screened, cartilage from a novel surgically induced model of OA in mice will be used in this study. We have developed micro dissection and linear mRNA amplification methods to overcome inherent problems with tissue availability from this small animal species. Successful completion of these studies will for the first time allow identification of the complex changes that occur in early OA. An important and likely outcome of this research will be identification of novel matrix proteins and regulatory molecules that will provide critical information for the development of new diagnostic and therapeutic approaches to OA.

澳大利亚15%的人口患有关节炎，60岁以上的人群中有50%患有关节炎。迄今为止，最常见的关节疾病是骨关节炎（OA）。骨性关节炎的主要特征之一是覆盖关节末端的软骨的破坏，这是长期结果的主要决定因素，需要进行关节置换手术。目前还没有能够阻止或逆转骨性关节炎软骨损伤的治疗方法。这主要是由于我们对软骨破裂的发生和进展所涉及的分子变化和途径的理解不完全。强大的新基因组方法允许同时筛选广泛基因的变化，特别是在人类和小鼠基因组完成测序后。通过将这项新技术应用于OA软骨退变的早期阶段，可以发现新基因的作用和参与该疾病发病过程的途径。然而，为了研究疾病开始时的变化，必须使用动物而不是人类关节组织，因为很难获得症状前的人类软骨。为了最大限度地筛选基因数量，本研究将使用一种新型手术诱导小鼠OA模型的软骨。我们已经开发了微解剖和线性mRNA扩增方法，以克服这种小动物物种组织可用性的固有问题。这些研究的成功完成将首次允许识别早期OA中发生的复杂变化。这项研究的一个重要和可能的结果将是鉴定新的基质蛋白和调节分子，这将为OA的新诊断和治疗方法的发展提供关键信息。