Evidence map›Paper›PMID 39695862›Full record

ArticleStem cell research & therapy2024

Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification.

Qinglu Tian, Shiqi Gao, Siying Li, Mian Wan, Xin Zhou, Wei Du, Xuedong Zhou, Liwei Zheng, Yachuan Zhou

Abstract read
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In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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  3. mInternational journal of molecular sciences · 2025
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4 · The record

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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.

Qinglu TianState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Shiqi GaoDepartment of Pediatric Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
Siying LiState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Mian WanState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Xin ZhouState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Wei DuState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Xuedong ZhouState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China.
Liwei ZhengState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China. liwei.zheng@scu.edu.cn.
Yachuan ZhouState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, Sichuan, China. zhouyc@scu.edu.cn.ORCID 0000-0002-5940-5534

Funding

National Natural Science Foundation of China 81800927National Natural Science Foundation of China 82170921
6 · The paper itself

Abstract

backgroundMulti-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate (αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence.

methodsWe employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism.

resultsHere we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix (ECM) function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation.

conclusionOur findings indicate that glutamine-αKG axis may epigenetically promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs and dentin regeneration, which provide a new research vision of potential dental tissue repairment therapy method or metabolite-based drug research.

Indexed as

Cell DifferentiationDentinGlutamineMesenchymal Stem CellsOsteogenesisAdenosineAnimalsDental PulpKetoglutaric AcidsMiceOdontogenesisRegenerationAdenosineGlutamineKetoglutaric AcidsASCsDentin regenerationEpigeneticGlutamine-αKG AxisIGF2Mesenchymal stem cells

Identifiers

PMID39695862
PMCPMC11657990

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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.