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：
10.1016/j.joca.2021.02.008
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发表时间：
2021-05
影响因子：
7
通讯作者：
Meng QJ
中科院分区：
文献类型：
--
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
髋关节和膝关节等关节的腕关节在24小时昼夜循环中经历重负荷和低负荷恢复的重复阶段。我们先前的工作已经显示了野生型小鼠软骨中转录水平的基因表达在昼夜之间的24小时节律性变化，这在生物钟敲除小鼠模型中丢失。然而，在这种富含基质的组织中，昼夜节律在多大程度上也调节蛋白质水平的基因表达仍然是未知的。我们通过48小时时间序列LC-MS/MS分析研究了小鼠股骨头关节软骨中蛋白质丰度的每日变化。在我们在所有时间点鉴定的1，177种蛋白质中，有145种蛋白质在股骨头软骨中的丰度显示出节律性变化。其中包括与关键软骨功能有关的分子，包括CTGF，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表现出一天中的时间依赖性功能。对已发表的软骨蛋白质组学数据集的分析显示，在骨关节炎和/或衰老中，有相当一部分节律蛋白质失调。我们的昼夜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转录方面而且在蛋白质丰度方面驱动昼夜节律。我们的研究结果清楚地呼吁考虑昼夜节律的计时机制，不仅在软骨生物学，而且在发病机制，治疗策略和生物标志物检测骨关节炎。
Cartilage in joints such as the hip and knee experiences repeated phases of heavy loading and low load recovery during the 24-h day/night cycle. Our previous work has shown 24 h rhythmic changes in gene expression at transcript level between night and day in wild type mouse cartilage which is lost in a circadian clock knock-out mouse model. However, it remains unknown to what extent circadian rhythms also regulate protein level gene expression in this matrix rich tissue. We investigated daily changes of protein abundance in mouse femoral head articular cartilage by performing a 48-h time-series LC-MS/MS analysis. Out of the 1,177 proteins we identified across all time points, 145 proteins showed rhythmic changes in their abundance within the femoral head cartilage. Among these were molecules that have been implicated in key cartilage functions, including CTGF, MATN1, PAI-1 and PLOD1 & 2. Pathway analysis revealed that protein synthesis, cytoskeleton and glucose metabolism exhibited time-of-day dependent functions. Analysis of published cartilage proteomics datasets revealed that a significant portion of rhythmic proteins were dysregulated in osteoarthritis and/or ageing. Our circadian proteomics study reveals that articular cartilage is a much more dynamic tissue than previously thought, with chondrocytes driving circadian rhythms not only in gene transcription but also in protein abundance. Our results clearly call for the consideration of circadian timing mechanisms not only in cartilage biology, but also in the pathogenesis, treatment strategies and biomarker detection in osteoarthritis.
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影响因子：
9.8
作者：
Jouffe C;Cretenet G;Symul L;Martin E;Atger F;Naef F;Gachon F
通讯作者：
Gachon F
温度调节可冷诱导的RNA结合蛋白基因CIRBP的剪接效率。
影响因子：
10.5
作者：
Gotic I;Omidi S;Fleury-Olela F;Molina N;Naef F;Schibler U
通讯作者：
Schibler U
影响因子：
4.8
作者：
Juhasz, Tumas;Matta, Csaba;Zakany, Roza
通讯作者：
Zakany, Roza
影响因子：
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作者：
Lee, RB;Urban, JPG
通讯作者：
Urban, JPG
影响因子：
10.5
作者：
Kojima, Shihoko;Sher-Chen, Elaine L.;Green, Carla B.
通讯作者：
Green, Carla B.