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

Overview of attention for article published in Journal of Biological Chemistry, August 2016
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Title
MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression*
Published in
Journal of Biological Chemistry, August 2016
DOI 10.1074/jbc.m116.737890
Pubmed ID
Authors

Spenser S Smith, Neha S Dole, Tiziana Franceschetti, Henry C Hrdlicka, Anne M Delany

Abstract

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 2 rhythmically expressed genes in calvaria, Igf1 and Hif1α;. 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. Lastly, 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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 17%
Student > Ph. D. Student 5 14%
Student > Master 5 14%
Student > Postgraduate 4 11%
Other 2 6%
Other 4 11%
Unknown 10 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 31%
Agricultural and Biological Sciences 6 17%
Medicine and Dentistry 2 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Immunology and Microbiology 1 3%
Other 3 8%
Unknown 12 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 May 2017.
All research outputs
#20,657,128
of 25,377,790 outputs
Outputs from Journal of Biological Chemistry
#80,170
of 85,237 outputs
Outputs of similar age
#277,261
of 355,244 outputs
Outputs of similar age from Journal of Biological Chemistry
#310
of 420 outputs
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