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下颌来源的细胞外囊泡通过靶向KDM2B调节小型猪的早期牙齿发育。

Mandible-derived extracellular vesicles regulate early tooth development in miniature swine via targeting KDM2B.

作者信息

Li Ye, Sun Meng, Ding Yi, Li Ang

机构信息

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.

Department of Periodontology, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.

出版信息

Int J Oral Sci. 2025 Apr 27;17(1):36. doi: 10.1038/s41368-025-00348-w.

DOI:10.1038/s41368-025-00348-w
PMID:40289114
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12034755/
Abstract

Tissue interactions play a crucial role in tooth development. Notably, extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential. Here, we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B. Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B, thereby regulating tooth development. An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice. In conclusion, this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization, which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.

摘要

组织相互作用在牙齿发育中起着至关重要的作用。值得注意的是，下颌骨与牙胚之间由细胞外囊泡介导的相互作用被认为是必不可少的。在此，我们揭示了下颌骨细胞外囊泡可通过调节组蛋白去甲基化酶KDM2B来调控牙间充质细胞的增殖和分化。进一步研究表明，源自下颌骨的细胞外囊泡可将miR-206传递给KDM2B，从而调节牙齿发育。一项动物研究表明，在裸鼠皮下移植八周后，miR-206/KDM2B通路影响牙齿形态发生和矿化。总之，本研究表明下颌骨在牙齿形态发生和矿化中起关键作用，这可能是牙齿发育异常的潜在治疗靶点以及牙齿再生的替代模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/1f167a004546/41368_2025_348_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/93a5594232d9/41368_2025_348_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/24a54cb6f530/41368_2025_348_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/bd50e18cb4b7/41368_2025_348_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/e8cd48c9005e/41368_2025_348_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/0821fafc2f30/41368_2025_348_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/75e07b2f3961/41368_2025_348_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/1f167a004546/41368_2025_348_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/93a5594232d9/41368_2025_348_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/24a54cb6f530/41368_2025_348_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/bd50e18cb4b7/41368_2025_348_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/e8cd48c9005e/41368_2025_348_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/0821fafc2f30/41368_2025_348_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/75e07b2f3961/41368_2025_348_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c42/12034755/1f167a004546/41368_2025_348_Fig7_HTML.jpg

相似文献

[1]
Mandible-derived extracellular vesicles regulate early tooth development in miniature swine via targeting KDM2B.

Int J Oral Sci. 2025-4-27

[2]
MicroRNA-211-5p in extracellular vesicles derived from BMSCs facilitates the repair of rat frozen shoulder via regulating KDM2B/LACC1 axis.

Tissue Cell. 2023-4

[3]
Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell-Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti-Inflammation Potentials.

Stem Cells. 2015-5-12

[4]
Marek's disease virus-encoded microRNA-M6-5p facilitates viral latent infection by targeting histone demethylase KDM2B.

J Virol. 2025-2-25

[5]
Inhibition of microRNA let-7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer.

Cancer Sci. 2021-1

[6]
Lysine-specific demethylase 2B (KDM2B)-let-7-enhancer of zester homolog 2 (EZH2) pathway regulates cell cycle progression and senescence in primary cells.

J Biol Chem. 2011-7-11

[7]
Spatial and temporal expression of histone demethylase, Kdm2a, during murine molar development.

Biotech Histochem. 2016

[8]
KDM2B mediates the Wnt/β-catenin pathway through transcriptional activation of PKMYT1 via microRNA-let-7b-5p/EZH2 to affect the development of non-small cell lung cancer.

Exp Cell Res. 2022-8-15

[9]
MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B.

Oncotarget. 2016-4-19

[10]
Reconstructing mandibular defects using autologous tissue-engineered tooth and bone constructs.

J Oral Maxillofac Surg. 2009-2

本文引用的文献

[1]
Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny.

Int J Oral Sci. 2023-11-24

[2]
Tooth agenesis: An overview of diagnosis, aetiology and management.

Jpn Dent Sci Rev. 2023-12

[3]
PAX9 mutations and genetic synergism in familial tooth agenesis.

Ann N Y Acad Sci. 2023-6

[4]
Context-specific regulation of extracellular vesicle biogenesis and cargo selection.

Nat Rev Mol Cell Biol. 2023-7

[5]
Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine.

Adv Healthc Mater. 2023-6

[6]
Mesenchymal condensation in tooth development and regeneration: a focus on translational aspects of organogenesis.

Physiol Rev. 2023-7-1

[7]
Tooth number abnormality: from bench to bedside.

Int J Oral Sci. 2023-1-6

[8]
Dental niche cells directly contribute to tooth reconstitution and morphogenesis.

Cell Rep. 2022-12-6

[9]
Epigenetic Regulation of Methylation in Determining the Fate of Dental Mesenchymal Stem Cells.

Stem Cells Int. 2022-9-22

[10]
The Role of Epigenetic in Dental and Oral Regenerative Medicine by Different Types of Dental Stem Cells: A Comprehensive Overview.

Stem Cells Int. 2022-6-9

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