Modulation of the Wnt signalling in the articular cartilage: is it all about the dose?

这个项目旨在研究维持关节软骨健康的关键机制，关节软骨是覆盖关节长骨边缘的组织，允许骨骼在我们移动时平滑滑动。在一种名为骨关节炎的疾病的发展过程中，关节软骨会受到严重的结构性损伤。骨关节炎影响着全球数百万人。受影响的人遭受慢性疼痛和残疾，生活质量严重下降。唯一可用的治疗方法是缓解疼痛，直到软骨损伤严重到需要手术。手术通常包括手术切除关节并用假体替换。通过了解保持软骨健康的机制，我们可以设计新的药物来在软骨丢失或受损的情况下重建软骨。我们已经有证据表明，一种名为Wnts(发音为wen z)的蛋白质对保持软骨的完整性很重要。因此，本应用程序的最终目标是了解这些WNT如何工作。我们有三个目标：1)阐明软骨细胞上存在的一组称为卷曲受体的受体中哪些其他蛋白质可能与WNTS一起工作；2)确定称为microRNAs的非常小的分子是否可以从细胞内改变WNTS的功能；3)确定WNTS的功能是否在OA的发育过程中发生改变，以及未来是否可以通过开发药物作为治疗方法来重新建立其原始活性。

This project aims to investigate key mechanisms maintaining the health of the articular cartilage, the tissue covering the edges of the long bones in the joint, allowing a smooth sliding of the bones while we move. The articular cartilage is affected by severe structural damage during the development of a disease called osteoarthritis. Osteoarthritis affects millions of people worldwide. People affected suffer chronic pain and disability with a severe decrease in the quality of life. The only available treatment is pain relief until cartilage damage is so severe that surgery is required. Surgery usually consists of surgical removal of the joint and its replacement with a prosthetic. By understanding the mechanisms keeping the cartilage healthy, we could design new drugs to re-establish the cartilage in cases where it is lost or damaged.We already have evidence showing that a class of proteins called Wnts (pronounced Wenz) are important to maintain cartilage integrity. Thus, the final goal of this application is to understand how these Wnts work. We have three aims: 1) to clarify which other proteins might work with the Wnts within a group of receptors, called frizzled receptors, which are present on cartilage cells; 2) to identify whether very small molecules called microRNAs can modify the function of the Wnts from within the cell; 3) determine whether the function of the Wnts is altered during OA development and whether re-establishing their original activity could be exploited in the future via development of a drug as a therapeutic treatment.