Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks
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PROVIDER: PRJEB61738 | ENA |
REPOSITORIES: ENA
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Project description: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 surges in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
2023-08-17 | E-MTAB-12877 | biostudies-arrayexpress
Project description: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.
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Project description:Daily (circadian) clocks are essential for regulating and coordinating physiology in mammals. Modulation of local chromatin structure has been shown for only a small number of genes, principally thought to be directly modulated by Clock-mediated histone acetylation. Here we show that genome-wide changes of active and suppressive histone marks control global chromatin architecture over the day and night. Examination of mouse liver tissue at 4 time-points around the clock in "free-running", continuous conditions (constant darkness, temperature and food available ad libitum).
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Project description:The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in peripheral tissues. While the hierarchy between the central and peripheral clocks is well established, peripheral clocks are largely viewed as a group and little is known regarding their specificity and functional organization. We employed feeding paradigms in conjunction with liver-specific clock-deficient murine model to map disparities and potential interactions between peripheral clocks. We found that peripheral clocks largely differ in their response to feeding-time. In view of its prominent role in nutrient processing, we hypothesized that the liver-clock instigate the response of peripheral clocks to feeding. Although the liver-clock did not affect the rhythmicity of clocks in other peripheral tissues, it strongly modulated their transcriptional rhythmicity upon daytime feeding. Overall, our findings suggest a role for the liver-clock in buffering feeding-related signals that affect rhythmicity of other peripheral tissues upon nutrient challenge, irrespective of their clocks.
2021-01-29 | GSE159135 | GEO
Project description:Organisms have adapted to the changing environmental conditions within the 24h cycle of the day by temporally segregating tissue physiology to the optimal time of the day. On the cellular level temporal segregation of physiological processes is established by the circadian clock, a Bmal1 dependent transcriptional oscillator network. The circadian clocks within individual cells of a tissue are synchronised by environmental signals, mainly light, in order to reach temporally segregated physiology on the tissue level. However, how light mediated synchronisation of peripheral tissue clocks is achieved mechanistically and whether circadian clocks in different organs are autonomous or interact with each other to achieve rhythmicity is unknown. Here we report that light can synchronise core circadian clocks in two peripheral tissues, the epidermis and liver hepatocytes, even in the complete absence of functional clocks in any other tissue within the whole organism. On the other hand, tissue extrinsic circadian clock rhythmicity is necessary to retain rhythmicity of the epidermal clock in the absence of light, proving for the first time that the circadian clockwork acts as a memory of time for the synchronisation of peripheral clocks in the absence of external entrainment signals. Furthermore, we find that tissue intrinsic Bmal1 is an important regulator of the epidermal differentiation process whose deregulation leads to a premature aging like phenotype of the epidermis. Thus, our results establish a new model for the segregation of peripheral tissue physiology whereby the synchronisation of peripheral clocks is acquired by the interaction of a light dependent but circadian clock independent pathway with circadian clockwork dependent cues.
2019-03-25 | GSE115104 | GEO