Evidence map›Paper›PMID 40200050›Full record

ArticleCommunications biology2025

METTL3 obstructs vascular smooth muscle cells osteogenic reprogramming by methylating Runx2 in chronic kidney disease.

Meijuan Cheng, Jingjing Jin, Dongxue Zhang, Mei Xiao, Hairong Zhao, Xiaoying Zhao, Shenglei Zhang, Yaling Bai, Jinsheng Xu

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. A RUNX2 reporter is expressed prior to osteochondral differentiation and models metaphyseal dysplasia with maxillary hypoplasia and brachydactyly.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026
    Article
  3. Review
  4. Review
  5. Article
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

9 authors.

Meijuan Cheng *Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.ORCID http://orcid.org/0000-0002-4376-5017
Jingjing Jin *Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.ORCID http://orcid.org/0000-0002-7666-2858
Dongxue ZhangDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Mei XiaoDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Hairong ZhaoDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Xiaoying ZhaoDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Shenglei ZhangDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Yaling BaiDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Jinsheng XuDepartment of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. xjs5766@126.com.ORCID http://orcid.org/0000-0001-7634-2232

Funding

Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation) H2023206385
6 · The paper itself

Abstract

The reprogrammed osteogenic phenotype of vascular smooth muscle cells (VSMCs) is considered a critical mechanism of vascular calcification (VC) in chronic kidney disease (CKD). Currently, the RNA N6-methyladenosine (m6A) modification is deciphered to be dynamically and reversibly participated in functional regulation of VSMCs. Here, we discover that serum m6A levels in RNA are dramatically reduced as VC progressed in patients with CKD, and this m6A demethylation is mainly due to the downregulation of methyltransferaselike-3 (METTL3). Functionally, METTL3 depletion exacerbates, whereas its overexpression attenuates calcification progression and osteogenic reprogramming. Mechanistically, Runx2, a crucial osteogenic gene, is identified as a key downstream target of METTL3-mediated m6A methylation. METTL3 negatively regulates Runx2 expression through the m6A modification. Overexpression of METTL3 exacerbates Runx2 mRNA degradation, which is orchestrated by the m6A reader YT521-B homology domain family 2 (YTHDF2) through specifically recognizing its m6A sites in the 3'UTR region. Finally, in vivo METTLs inhibitor SAH treatment aggravates VC and osteogenic conversion in aortas of CKD rats, accompanied by Runx2 expression upregulation. These above data reveal an underlying mechanism by which the m6A writer METTL3 regulates Runx2 expression through YTHDF2-mediated mRNA degradation and suggest a potential therapeutic strategy to reverse the osteogenic reprogramming of VSMCs.

Indexed as

Cellular ReprogrammingCore Binding Factor Alpha 1 SubunitMethyltransferasesMuscle, Smooth, VascularMyocytes, Smooth MuscleOsteogenesisRenal Insufficiency, ChronicAdenosineAnimalsHumansMaleMethylationRatsRats, Sprague-DawleyVascular CalcificationAdenosineCore Binding Factor Alpha 1 SubunitMethyltransferasesMETTL3 protein, humanN-methyladenosineRUNX2 protein, humanRunx2 protein, rat

Identifiers

PMID40200050
PMCPMC11978862

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.