Evidence map›Paper›PMID 33424022›Full record

ArticleBone research2021

MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS.

Takayuki Fujii, Koichi Murata, Se-Hwan Mun, Seyeon Bae, Ye Ji Lee, Tannia Pannellini, Kyuho Kang, David Oliver, Kyung-Hyun Park-Min, Lionel B Ivashkiv

Open access · goldAbstract read
In one paragraph

Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

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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

10 authors at 1 institution in 3 countries.

Takayuki FujiiArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Koichi MurataArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Se-Hwan MunArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Seyeon BaeArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Ye Ji LeeArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Tannia PannelliniArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Kyuho KangArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
David OliverArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA.
Kyung-Hyun Park-MinArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA. parkmink@hss.edu.ORCID http://orcid.org/0000-0002-0208-6341
Lionel B IvashkivArthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 10021, USA. ivashkivl@hss.edu.
Hospital for Special Surgery · US

Funding

STEROID THERAPY AND CYTOKINES IN RHEUMATIC DISEASESR01AI046712 · NIAID · HOSPITAL FOR SPECIAL SURGERY · PI IVASHKIV, LIONEL B · 2000 to 2025
$12.5M
Inhibition of STAT3 and inflammatory cytokine productionR01AI044938 · NIAID · HOSPITAL FOR SPECIAL SURGERY · PI IVASHKIV, LIONEL B · 2000 to 2025
$9.2M
Negative Regulation of OsteoclastogenesisR01DE019420 · NIDCR · HOSPITAL FOR SPECIAL SURGERY · PI IVASHKIV, LIONEL B · 2008 to 2022
$6.0M
The Crosstalk between MYC and Metabolism during OsteoclastogenesisR01AR069562 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI PARK-MIN, KYUNG-HYUN · 2016 to 2020
$1.9M
A novel regulating pathway in osteoclastogenesis and arthritic bone resorptionR01AR073156 · NIAMS · HOSPITAL FOR SPECIAL SURGERY · PI PARK-MIN, KYUNG-HYUN · 2018 to 2022
$1.9M
NIAID NIH HHS R01 AI044938NIAID NIH HHS R01 AI046712NIAMS NIH HHS R01 AR073156NIDCR NIH HHS R01 DE019420U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5R01 AR069562U.S. Department of Health & Human Services | National Institutes of Health (NIH) 5R01 AR073156
6 · The paper itself

Abstract

Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation, which results in decreased bone mineral density. The MEF2C locus, which encodes the transcription factor MADS box transcription enhancer factor 2, polypeptide C (MEF2C), is strongly associated with adult osteoporosis and osteoporotic fractures. Although the role of MEF2C in bone and cartilage formation by osteoblasts, osteocytes, and chondrocytes has been studied, the role of MEF2C in osteoclasts, which mediate bone resorption, remains unclear. In this study, we identified MEF2C as a positive regulator of human and mouse osteoclast differentiation. While decreased MEF2C expression resulted in diminished osteoclastogenesis, ectopic expression of MEF2C enhanced osteoclast generation. Using transcriptomic and bioinformatic approaches, we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1, which play a key role in osteoclastogenesis. Mechanistically, MEF2C binds to FOS regulatory regions to induce c-FOS expression, leading to the activation of NFATC1 and downstream osteoclastogenesis. Inducible deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis, a murine model of inflammatory arthritis. Our findings reveal direct regulation of osteoclasts by MEF2C, thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.

Identifiers

PMID33424022
PMCPMC7797478
OpenAlexW3119970908

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.