RT Journal Article
SR Electronic
T1 Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.01.462769
DO 10.1101/2021.10.01.462769
A1 Michal Dudek
A1 Dharshika Pathiranage
A1 Cátia F. Gonçalves
A1 Craig Lawless
A1 Dong Wang
A1 Zhuojing Luo
A1 Liu Yang
A1 Farshid Guilak
A1 Judith Hoyland
A1 Qing-Jun Meng
YR 2021
UL http://biorxiv.org/content/early/2021/10/18/2021.10.01.462769.abstract
AB Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light). Presence of niche-dependent physiological time cues has been proposed, allowing local tissues flexibility of phase adjustment. However, to date, such stimuli have remained elusive. Here we show that cycles of mechanical loading and osmotic stimuli within physiological range drive rhythmic expression of clock genes and reset clock phase and amplitude in cartilage and intervertebral disc tissues. Hyperosmolarity (not hypo-osmolarity) resets clocks in young and ageing skeletal tissues through mTORC2-AKT-GSK3β pathway, leading to genome-wide induction of rhythmic genes. These results advocate diurnal patterns of mechanical loading and consequent daily surges in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.One-Sentence Summary Circadian clocks in aneural skeletal tissues sense the passage of time through rhythmic patterns of loading and osmolarityCompeting Interest StatementThe authors have declared no competing interest.