Evidence map›Paper›PMID 31896234›Full record

ArticleMolecules and cells2020

Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway.

Kabsun Kim, Jung Ha Kim, Inyoung Kim, Semun Seong, Nacksung Kim

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecules and cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  16. Co-regulation of circadian clock genes and microRNAs in bone metabolism.Journal of Zhejiang University. Science. B · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kabsun KimDepartment of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
Jung Ha KimDepartment of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
Inyoung KimDepartment of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
Semun SeongDepartment of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
Nacksung KimDepartment of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Korea.
Chonnam National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Reverbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo . Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.

Indexed as

AnimalsBone RemodelingBone ResorptionCell DifferentiationCells, CulturedCircadian ClocksDisease Models, AnimalGain of Function MutationHumansMaleMiceMice, Inbred ICRNuclear Receptor Subfamily 1, Group D, Member 1OsteoblastsOsteoclastsOsteogenesisNr1d1 protein, mouseNr1d2 protein, mouseNuclear Receptor Subfamily 1, Group D, Member 1p38 Mitogen-Activated Protein KinasesReceptors, Cytoplasmic and NuclearRepressor ProteinsRNA, Small Interferingbone remodelingosteoblastosteoclastp38 MAPKRev-erb

Identifiers

PMID31896234
PMCPMC6999712
OpenAlexW3002311736

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.