Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.
Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.
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机械载荷和高渗透度作为骨骼昼夜节律时钟的每日重置提示。
DOI：
10.1038/s41467-023-42056-1
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发表时间：
2023-11-14
影响因子：
16.6
通讯作者：
Meng, Qing-Jun
中科院分区：
文献类型：
--
作者：
Dudek, Michal;Pathiranage, Dharshika R. J.;Bano-Otalora, Beatriz;Paszek, Anna;Rogers, Natalie;Goncalves, Catia F.;Lawless, Craig;Wang, Dong;Luo, Zhuojing;Yang, Liu;Guilak, Farshid;Hoyland, Judith A.;Meng, Qing-Jun
哺乳动物行为和生理的日常节律是由一个多振荡器昼夜节律系统产生的，该系统通过环境线索（例如光线和摄食）进行传递。已经提出了组织壁龛依赖的生理时间线索的存在，允许组织基于局部信号进行昼夜节律相位调节的能力。然而，到目前为止，这样的刺激仍然难以捉摸。在这里，我们表明在生理范围内的机械负荷和相关渗透挑战的日常模式重置了体内软骨和椎间盘组织和组织外植体培养中的生物钟阶段和振幅。高渗透压（但不是低渗透压）重置年轻和衰老骨骼组织中的时钟，并诱导细胞中节律基因的全基因组表达。在机制上，RNAseq和生化分析显示PLD2-mTORC2-AKT-GSK3β轴是体内负荷和高渗诱导的时钟变化的趋同途径。这些结果揭示了机械负荷的日模式和随之而来的渗透压的日振荡作为一个真正的组织龛特异性时间线索，以保持骨骼昼夜节律同步。软骨和椎间盘中的24小时生物钟在调节组织生理方面发挥着关键作用，但它们如何在日常基础上被重置仍是一个谜。在这里，作者表明，机械负荷的日常模式和相关的渗透压变化为这些骨骼时钟提供了组织类型特定的夹带时间线索。
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. The 24-hour circadian clocks in cartilage and intervertebral disc play key roles in regulating tissue physiology, yet how they are reset on a daily basis remains elusive. Here the authors show that daily patterns of mechanical loading and associated changes in osmolarity provide a tissue-type specific entrainment time cue for these skeletal clocks.
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DOI：
10.1073/pnas.1719298115
发表时间：
2018-04-03
影响因子：
11.1
作者：
Imamura K;Yoshitane H;Hattori K;Yamaguchi M;Yoshida K;Okubo T;Naguro I;Ichijo H;Fukada Y
通讯作者：
Fukada Y
影响因子：
--
作者：
Gossan, Nicole;Zeef, Leo;Hensman, James;Hughes, Alun;Bateman, John F.;Rowley, Lynn;Little, Christopher B.;Piggins, Hugh D.;Rattray, Magnus;Boot-Handford, Raymond P.;Meng, Qing-Jun
通讯作者：
Meng, Qing-Jun
影响因子：
4.6
作者：
Belavý DL;Quittner MJ;Ridgers N;Ling Y;Connell D;Rantalainen T
通讯作者：
Rantalainen T
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S
影响因子：
56.9
作者：
Balsalobre, A;Brown, SA;Schibler, U
通讯作者：
Schibler, U