The 4th dimension and adult stem cells: Can timing be everything?

Gimble, Jeffrey M.; Floyd, Z. Elizabeth; Bunnell, Bruce A.

doi:10.1002/jcb.22153

Cited by 28 publications

(37 citation statements)

References 121 publications

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“…This acetylation attenuates the binding of the GR to GREs, limiting its actions. In peripheral tissues, the BMAL1/CLOCK-mediated counterregulation of glucocorticoid signaling provides a mechanism to prevent overexposure of target tissues to glucocorticoids at times when serum levels of glucocorticoid are at their peak (1). Similarly, we demonstrate that miR-433 activity blunts glucocorticoid signaling.…”

Section: Discussionsupporting

confidence: 50%

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MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

Smith

Dole²,

Franceschetti³

et al. 2016

Journal of Biological Chemistry

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Serum glucocorticoids play a critical role in synchronizing circadian rhythm in peripheral tissues, and multiple mechanisms regulate tissue sensitivity to glucocorticoids. In the skeleton, circadian rhythm helps coordinate bone formation and resorption. Circadian rhythm is regulated through transcriptional and post-transcriptional feedback loops that include microRNAs . How microRNAs regulate circadian rhythm in bone is unexplored. We show that in mouse calvaria, miR-433 displays robust circadian rhythm, peaking just after dark. In C3H/10T1/2 cells synchronized with a pulse of dexamethasone, inhibition of miR-433 using a tough decoy altered the period and amplitude of Per2 gene expression, suggesting that miR-433 regulates rhythm. Although miR-433 does not directly target the Per2 3-UTR, it does target two rhythmically expressed genes in calvaria, Igf1 and Hif1␣. miR-433 can target the glucocorticoid receptor; however, glucocorticoid receptor protein abundance was unaffected in miR-433 decoy cells. Rather, miR-433 inhibition dramatically enhanced glucocorticoid signaling due to increased nuclear receptor translocation, activating glucocorticoid receptor transcriptional targets. Last, in calvaria of transgenic mice expressing a miR-433 decoy in osteoblastic cells (Col3.6 promoter), the amplitude of Per2 and Bmal1 mRNA rhythm was increased, confirming that miR-433 regulates circadian rhythm. miR-433 was previously shown to target Runx2, and mRNA for Runx2 and its downstream target, osteocalcin, were also increased in miR-433 decoy mouse calvaria. We hypothesize that miR-433 helps maintain circadian rhythm in osteoblasts by regulating sensitivity to glucocorticoid receptor signaling.The circadian rhythm is an internal timing mechanism important for orchestrating physiological homeostasis, through synchronizing behavioral and physiological patterns. This coordinates biological processes critical for overall health, such as tissue repair and growth, maintenance of the immune response, and optimization of metabolism. The circadian rhythm is driven by a complex interaction between the hypothalamic suprachiasmatic nucleus (SCN), 4 also known as the central clock, and the peripheral circadian clocks. As the central oscillator, the SCN responds to environmental periodic cues, such as light, eating patterns, and temperature. In response to these cues, the SCN entrains peripheral circadian clocks through stimulation of neural or hormonal signals (e.g. glucocorticoids) to enact their effects on target tissues (1).In the central oscillator and peripheral tissues, the rhythm is maintained locally by clock genes that interact through transcriptional and post-transcriptional feedback loops. The main positive regulators are aryl hydrocarbon receptor nuclear translocator-like (Arntl or Bmal1) and circadian locomotor output cycles kaput (Clock), which are negatively regulated by the period genes (Per1, Per2, and Per3) and the cryptochrome genes (Cry1 and Cry2), among others (for a review, see Ref.2). Bmal1 and Clock form a heterodi...

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Section: Discussionsupporting

confidence: 50%

“…In response to these cues, the SCN entrains peripheral circadian clocks through stimulation of neural or hormonal signals (e.g. glucocorticoids) to enact their effects on target tissues (1).…”

mentioning

confidence: 99%

MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

Smith

Dole²,

Franceschetti³

et al. 2016

Journal of Biological Chemistry

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“…Oscillations in proliferative activity and recruitment of hematopoietic progenitor cells have been demonstrated in mammals. 41,42 Although vertebrate PROKs have been assigned a role as an suprachiasmatic nucleus output molecule, no role in regulating rhythmic oscillations in hematopoiesis has been proposed, and the expression pattern of Ast1 suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Therefore, it should be of interest to see whether any PROK has such a role in vertebrate hematopoiesis.…”

Section: Crustacean Hematopoiesis Is Rhythmically Controlledmentioning

confidence: 99%

Crustacean hematopoiesis and the astakine cytokines

Lin

Söderhäll

2011

Blood

197

159

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“…This ability to respond to environmental daily rhythms has been conserved along evolution and is found among species from bacteria to mammals [1]. The circadian clock mechanism is regulated by a highly conserved set of genes encoding regulatory proteins.…”

Section: Introductionmentioning

confidence: 99%

An ancient cytokine, astakine, mediates circadian regulation of invertebrate hematopoiesis

Watthanasurorot

Söderhäll

Jiravanichpaisal

et al. 2010

Cell. Mol. Life Sci.

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Invertebrate circulating hemocytes are key players in the innate immune defense and their continuous renewal from hematopoietic tissues is tightly regulated in crustaceans by astakine, a new family of cytokines sharing a prokineticin (PROK) domain. In vertebrates, brain PROKs function as transmitters of circadian rhythms and we present evidence that hemocyte release from hematopoietic tissues in crayfish is under circadian regulation, a direct result of rhythmic expression of astakine. We demonstrate that the observed variation in astakine expression has an impact on innate immunity assessed as susceptibility to a pathogenic Pseudomonas species. These findings enlighten the importance of comparing immune responses at fixed times not to neglect circadian regulation of innate immunity. Moreover, our results entail an evolutionary conserved function for prokineticins as mediators of circadian rhythm, and for the first time show a role for this domain in circadian regulation of hematopoiesis that may have implications also in vertebrates.

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The 4th dimension and adult stem cells: Can timing be everything?

Cited by 28 publications

References 121 publications

MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

Crustacean hematopoiesis and the astakine cytokines

An ancient cytokine, astakine, mediates circadian regulation of invertebrate hematopoiesis

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