Evidence map›Paper›PMID 41402268›Full record

ArticleNature communications2025

TRIM37-PARP1-TET1 axis maintains stemness and prevents osteoporosis by inhibiting DNMT1 alternative splicing via 5hmC regulation.

Chun-Te Ho, Ling-Hui Li, Wei-Chao Chang, Heng-Hsiung Wu, Ya-Huey Chen, Shih-Chieh Hung

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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. Article
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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

6 authors.

Chun-Te HoDrug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Ling-Hui LiInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Wei-Chao ChangCenter for Molecular Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Heng-Hsiung WuDrug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Ya-Huey ChenDrug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Shih-Chieh HungDrug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. hung3340@gmail.com.ORCID http://orcid.org/0000-0003-1813-4616

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The significance of DNA hydroxymethylation in replicative senescence of mesenchymal stem cells (MSCs) and aging-related osteoporosis remains unknown. Here, we reveal 5hmC levels positively regulate MSC self-renewal and osteoblast differentiation. Mechanistically, PARP1 recruits TET1 to hydrolyze methylated nucleotides on DNMT1 exons, aiding CTCF in preventing DNMT1 alternative splicing in early MSCs. Additionally, ATM phosphorylates TRIM37 at Th203, promoting its nuclear entry and the monoubiquitination of PARP1, stabilizing the protein. CTCF or TRIM37 knockdown induces replicative senescence of MSCs with loss of full-length DNMT1. Co-treatment with resveratrol (ATM activator) and vitamin C (TET1 activator) rejuvenates late MSCs via the TRIM37/PARP1/DNMT1 pathway and alleviates osteoporosis in aged mice. Gene knockout experiments further reveal the participation of TRIM37 and PARP1 in MSC aging, contributing significantly to bone maintenance and repair in vivo. This study emphasizes the role of DNA hydroxymethylation in stemness, suggesting therapeutic strategies, especially for osteoporosis.

Indexed as

Alternative SplicingDNA (Cytosine-5-)-Methyltransferase 1OsteoporosisPoly (ADP-Ribose) Polymerase-1Proto-Oncogene ProteinsTripartite Motif ProteinsUbiquitin-Protein LigasesAnimalsCell DifferentiationCellular SenescenceDNA-Binding ProteinsDNA MethylationHumansMaleMesenchymal Stem CellsMiceDNA-Binding ProteinsDNA (Cytosine-5-)-Methyltransferase 1Dnmt1 protein, mouseParp1 protein, mousePoly (ADP-Ribose) Polymerase-1Proto-Oncogene ProteinsTET1 protein, mouseTripartite Motif ProteinsUbiquitin-Protein Ligases

Identifiers

PMID41402268
PMCPMC12748648

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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.