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

影响人体骨骼和关节的疾病范围很广，从由单一基因突变引起的罕见疾病（单基因骨病）到由多种因素引起的常见疾病，包括复杂的基因突变、损伤和生活方式的综合影响。罕见和常见的骨骼疾病有许多共同的特征和疾病途径。因此，人们早就认识到，研究罕见骨骼疾病的疾病过程可以帮助我们理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来研究一组罕见的人类骨骼疾病的疾病过程，这些疾病也会导致骨关节炎（OA）和另一种疼痛的疾病，即骨软骨炎（OCD），这种疾病主要影响儿童。我们已经证明，特定的畸形结构蛋白——软骨的组成部分——会导致软骨的形成方式出现问题，从而使软骨更容易患上OA和强迫症。因此，我们计划更详细地研究这些基因工程小鼠的人类骨病“模型”，以了解疾病过程，这将最终使我们能够开发出针对这些目前无法治愈的常见疾病的新疗法。

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.