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

Autor: Dudek M; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Pathiranage DRJ; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Bano-Otalora B; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK., Paszek A; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Rogers N; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Gonçalves CF; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Lawless C; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Wang D; Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Luo Z; Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Yang L; Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Guilak F; Department of Orthopedic Surgery and Department of Biomedical Engineering, Center of Regenerative Medicine, Washington University, St. Louis, MO, 63110, USA.; Shriners Hospitals for Children - St. Louis, St. Louis, MO, 63110, USA., Hoyland JA; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Judith.A.Hoyland@manchester.ac.uk.; NIHR Manchester Biomedical Research Centre, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Judith.A.Hoyland@manchester.ac.uk., Meng QJ; Wellcome Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK. Qing-Jun.Meng@manchester.ac.uk.; Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, UK. Qing-Jun.Meng@manchester.ac.uk.; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Qing-Jun.Meng@manchester.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 14; Vol. 14 (1), pp. 7237. Date of Electronic Publication: 2023 Nov 14.
DOI: 10.1038/s41467-023-42056-1
Abstrakt: Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily oscillations in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
(© 2023. The Author(s).)
Databáze: MEDLINE
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