How do circadian clocks in chondrocytes contribute to cartilage function in health and disease

软骨细胞中的生物钟如何影响健康和疾病中的软骨功能

• 批准号: MR/K019392/1
• 负责人: Qing-Jun Meng
• 金额: $ 51.73万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK019392%2F1
• 关键词: How; do; circadian; clocks; chondrocytes

This research focuses on the molecular/cellular mechanisms of biological clocks in the joint cartilage and their contributions to the development and severity of damage in osteoarthritis (OA). Circadian (about a day) clocks are endogenous time pieces in our bodies that are responsible for generating 24 hour rhythms in behaviour and physiology. Disruptions of circadian rhythms by advanced age, shift work or jet lag can have severe impacts on body functions and disease risks. By culturing chondrocyte cells (the only cell type in cartilage) in petri dishes, isolating cartilage pieces, and a surgical operation which mimics OA in clock disrupted mouse knee joint, we expect to unravel: 1) Which rhythmic genes in cartilage rely on the local chondrocyte clock to maintain their circadian pattern of expression? 2) Can we target cartilage circadian clock proteins as a novel approach to alter chondrocyte gene expression? 3) Do alterations in specific components of the clock mechanism cause early onset OA, or leave mice more susceptible to surgical injury-induced OA? This project will generate new data and knowledge that will benefit researchers working on circadian biology, chondrocyte biology, ageing and joint diseases. It is also likely to benefit pharmaceutical industries who are interested in developing new approaches to targeting arthritic diseases. Outcomes will advance our understanding of the role circadian rhythms play in the healthy state of the joint cartilage, so will also be of value to the general public.

本研究的重点是关节软骨中生物钟的分子/细胞机制及其对骨关节炎（OA）损伤的发展和严重程度的贡献。生理时钟（大约一天）是我们体内的内源性时间片段，负责在行为和生理上产生24小时的节奏。高龄、倒班或时差导致的昼夜节律紊乱会对身体功能和疾病风险产生严重影响。通过在培养皿中培养软骨细胞（软骨中唯一的细胞类型），分离软骨碎片，以及模拟时钟中断小鼠膝关节OA的外科手术，我们希望揭示：1)软骨中哪些节律性基因依赖局部软骨细胞时钟来维持其昼夜节律表达模式？2)我们能否将软骨生物钟蛋白作为一种改变软骨细胞基因表达的新方法？3)时钟机制的特定组成部分的改变会导致早发性OA，还是使小鼠更容易发生手术损伤性OA？该项目将产生新的数据和知识，这将有利于研究昼夜节律生物学、软骨细胞生物学、衰老和关节疾病的研究人员。这也可能使制药行业受益，他们对开发针对关节炎疾病的新方法感兴趣。结果将促进我们对昼夜节律在关节软骨健康状态中所起作用的理解，因此对公众也有价值。

项目成果

Circadian time series proteomics reveals daily dynamics in cartilage physiology.

• DOI: 10.1016/j.joca.2021.02.008
• 发表时间: 2021-05
• 期刊: Osteoarthritis and cartilage
• 影响因子: 7
• 作者: Dudek M;Angelucci C;Pathiranage D;Wang P;Mallikarjun V;Lawless C;Swift J;Kadler KE;Boot-Handford RP;Hoyland JA;Lamande SR;Bateman JF;Meng QJ
• 通讯作者: Meng QJ

Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.

机械载荷和高渗透度作为骨骼昼夜节律时钟的每日重置提示。

• DOI: 10.1038/s41467-023-42056-1
• 发表时间: 2023-11-14
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Dudek, Michal;Pathiranage, Dharshika R. J.;Bano-Otalora, Beatriz;Paszek, Anna;Rogers, Natalie;Goncalves, Catia F.;Lawless, Craig;Wang, Dong;Luo, Zhuojing;Yang, Liu;Guilak, Farshid;Hoyland, Judith A.;Meng, Qing-Jun
• 通讯作者: Meng, Qing-Jun

Running on time: the role of circadian clocks in the musculoskeletal system.

• DOI: 10.1042/bj20140700
• 发表时间: 2014-10-01
• 期刊: The Biochemical journal
• 作者: Dudek M;Meng QJ
• 通讯作者: Meng QJ