Defining the role of aggrecan and type IX collagen in osteoarthritis and osteochondritis dissecans through in vivo studies of genetic bone diseases

通过遗传性骨病的体内研究确定聚集蛋白聚糖和 IX 型胶原蛋白在骨关节炎和剥脱性骨软骨炎中的作用

• 批准号: MR/X001873/1
• 负责人: Michael Briggs
• 金额: $ 82.61万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX001873%2F1
• 关键词: Defining; role; aggrecan; type; IX

Diseases that affect the bones and joints of the human body can range from rare diseases, which result from mutations in a single gene (monogenetic bone diseases) to common conditions that result from a number of factors including a combination of complex genetic mutations, injury and lifestyle. Rare and common skeletal diseases share many features and disease pathways in common. It is therefore long recognised that studying disease processes in the rare skeletal diseases can help our understanding of disease processes in common conditions such as arthritis.To this end we have been using genetically engineered mice to study disease processes in a group of rare human bone diseases, which also cause osteoarthritis (OA) and another painful condition known as osteochondritis dissecans (OCD), a disease that primarily affects children. We have shown that specific malformed structural proteins - the building blocks of cartilage - can cause problems with the way that cartilage is made and this renders it more susceptible to OA and OCD. We therefore plan to study these genetically engineered mice 'models' of human bone disease in greater detail, to understand disease process, which will eventually allow us to develop new therapies for these currently incurable common diseases.

影响人体骨骼和关节的疾病可以从罕见疾病（由单个基因突变引起）（单基因骨骼疾病）到由多种因素引起的常见疾病，包括复杂的基因突变，损伤和生活方式的组合。罕见和常见骨骼疾病有许多共同的特征和疾病途径。因此，长期以来，研究罕见骨骼疾病的疾病过程可以帮助我们了解关节炎等常见疾病的疾病过程。为此，我们一直在使用基因工程小鼠研究一组罕见人类骨骼疾病的疾病过程，这些疾病也会导致骨关节炎（OA）和另一种称为剥脱性骨软骨炎（OCD）的疼痛状况，主要影响儿童的疾病我们已经证明，特定的畸形结构蛋白质-软骨的构建模块-可以导致软骨的形成方式出现问题，这使得它更容易患OA和OCD。因此，我们计划更详细地研究这些人类骨骼疾病的基因工程小鼠“模型”，以了解疾病过程，这最终将使我们能够为这些目前无法治愈的常见疾病开发新的疗法。