Circadian time series proteomics reveals daily dynamics in cartilage physiology

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 spectro...

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Bibliographic Details
Published inbioRxiv
Main Authors Dudek, Michal, Angelucci, Constanza, Jayalath Pd Ruckshanthi, Wang, Ping, Venkatesh Mallikarjun, Lawless, Craig, Kadler, Karl E, Hoyland, Judith A, Lamande, Shireen R, Bateman, John F, Qing-Jun, Meng
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 31.05.2019
Subjects
Aging
Arthritis
Bioinformatics
Cartilage (articular)
Cartilage diseases
Chondrocytes
Circadian rhythms
Connective tissue growth factor
Cytoskeleton
Femur
Gene expression
Glucose metabolism
Mass spectroscopy
Osteoarthritis
Protein biosynthesis
Protein turnover
Proteins
Proteomics
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Summary: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.
DOI:10.1101/654855