Circadian time series proteomics reveals daily dynamics in cartilage physiology
Circadian time series proteomics reveals daily dynamics in cartilage physiology
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DOI：
10.1101/654855
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发表时间：
2019-05
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影响因子：
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通讯作者：
M. Dudek;C. Angelucci;J. P. Ruckshanthi;Ping Wang;V. Mallikarjun;C. Lawless;J. Swift;K. Kadler;J. Hoyland;S. Lamandé;J. Bateman;Q. Meng
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作者：
M. Dudek;C. Angelucci;J. P. Ruckshanthi;Ping Wang;V. Mallikarjun;C. Lawless;J. Swift;K. Kadler;J. Hoyland;S. Lamandé;J. Bateman;Q. Meng
目的关节软骨在24小时昼夜循环中经历周期性的重负荷和低负荷恢复。采用24小时时间序列蛋白质组学方法，研究小鼠股骨头关节软骨蛋白质丰度的日变化。方法采用串联质谱法对小鼠软骨中蛋白质进行定量分析。进行生物信息学分析以量化蛋白质丰度的节律性变化。分离并培养原代软骨细胞，以独立验证所选节律蛋白。结果共检测到145个节律蛋白。其中包括关键的软骨分子，包括CCN 2，MATN 1，派-1和PLOD 1和2。途径分析表明，蛋白质合成，细胞骨架和葡萄糖代谢相关的蛋白质表现出一天中的时间依赖性峰的丰度。对已发表的关节软骨蛋白质组学数据集的荟萃分析显示，许多节律蛋白在骨关节炎和/或衰老中失调。结论：我们的昼夜节律蛋白质组学研究表明，关节软骨是一个比以前认为的更具活力的组织。软骨细胞不仅在基因表达方面而且在蛋白质丰度方面表现出昼夜节律。我们的研究结果清楚地呼吁在理解软骨生物学、骨关节炎发病机制、治疗策略和生物标志物检测时考虑昼夜节律。
Objectives Articular cartilage undergoes cyclical heavy loading and low load recovery during the 24-hour day/night cycle. We investigated the daily changes of protein abundance in mouse femoral head articular cartilage by performing 24-hour time-series proteomics study. Methods Tandem mass spectrometry analysis was used to quantify proteins extracted from mouse cartilage. Bioinformatics analysis was performed to quantify rhythmic changes in protein abundance. Primary chondrocytes were isolated and cultured for independent validation of selected rhythmic proteins. Results 145 rhythmic proteins were detected. Among these were key cartilage molecules including CCN2, MATN1, PAI-1 and PLOD1 & 2. Pathway analysis revealed that proteins related to protein synthesis, cytoskeleton and glucose metabolism exhibited time-of-day dependent peaks in their abundance. Meta-analysis of published proteomics datasets from articular cartilage revealed that numerous rhythmic proteins were dysregulated in osteoarthritis and/or ageing. Conclusions Our circadian proteomics study revealed that articular cartilage is a much more dynamic tissue than previously thought. Chondrocytes exhibit circadian rhythms not only in gene expression but also in protein abundance. Our results clearly call for the consideration of circadian timing in understanding cartilage biology, osteoarthritis pathogenesis, treatment strategies and biomarker detection.