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源自牙囊干细胞的细胞外囊泡通过抑制破骨细胞分化来调节牙齿萌出。

Extracellular vesicles derived from dental follicle stem cells regulate tooth eruption by inhibiting osteoclast differentiation.

作者信息

Sun Meng, Yu Yiru, Zhang Weixing, Ding Yi, Li Ang, Li Ye

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, Shaanxi, China.

出版信息

Front Cell Dev Biol. 2024 Dec 20;12:1503481. doi: 10.3389/fcell.2024.1503481. eCollection 2024.

DOI:10.3389/fcell.2024.1503481
PMID:39834384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11744031/
Abstract

Tooth eruption as a crucial part in tooth development and regeneration is accompanied by ongoing osteogenesis and osteoclast activity. The dental follicle (DF) surrounding the developing tooth harbors dental follicle stem cells (DFSCs) which play a crucial role in maintaining bone remodeling. However, the mechanisms through which they regulate the balance between osteogenesis and osteoclast activity during tooth eruption remain poorly understood. Notably, extracellular vesicles (EVs) in bone homeostasis are considered essential. Our study revealed that the DFSCs could modulate tooth eruption by inhibiting osteoclast differentiation via EVs. Further investigation showed that EVs from DFSCs could inhibit osteoclast differentiation through the ANXA1-PPARγ-CEBPα pathway. Animal experiments indicated that EVs from DFSCs and the cargo ANXA1 affected tooth eruption. In summary, this study suggests the critical role of the dental follicle in tooth eruption through EVs, which may provide therapeutic targets for abnormal tooth eruption and effective approaches for the eruption of regenerated teeth.

摘要

牙齿萌出作为牙齿发育和再生的关键部分,伴随着持续的成骨作用和破骨细胞活性。发育中牙齿周围的牙囊(DF)含有牙囊干细胞(DFSCs),它们在维持骨重塑中起关键作用。然而,在牙齿萌出过程中,它们调节成骨作用和破骨细胞活性之间平衡的机制仍知之甚少。值得注意的是,细胞外囊泡(EVs)在骨稳态中被认为是必不可少的。我们的研究表明,DFSCs可以通过EVs抑制破骨细胞分化来调节牙齿萌出。进一步的研究表明,来自DFSCs的EVs可以通过ANXA1-PPARγ-CEBPα途径抑制破骨细胞分化。动物实验表明,来自DFSCs的EVs和货物ANXA1会影响牙齿萌出。总之,本研究表明牙囊通过EVs在牙齿萌出中起关键作用,这可能为异常牙齿萌出提供治疗靶点,并为再生牙齿的萌出提供有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/5714ef116288/fcell-12-1503481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/fd612d53192c/FCELL_fcell-2024-1503481_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/654a1c7b4673/fcell-12-1503481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/0846847582fb/fcell-12-1503481-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/d75598baa935/fcell-12-1503481-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/6e0d40a0c3d9/fcell-12-1503481-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/5714ef116288/fcell-12-1503481-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/fd612d53192c/FCELL_fcell-2024-1503481_wc_abs.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/654a1c7b4673/fcell-12-1503481-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/0846847582fb/fcell-12-1503481-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/d75598baa935/fcell-12-1503481-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/6e0d40a0c3d9/fcell-12-1503481-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9245/11744031/5714ef116288/fcell-12-1503481-g005.jpg

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本文引用的文献

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Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.与原发性牙萌出失败中PTH1R相关的病因机制及遗传/生物学调节
Calcif Tissue Int. 2024 Aug;115(2):101-116. doi: 10.1007/s00223-024-01227-y. Epub 2024 Jun 4.
2
Deciphering the Heterogeneity Landscape of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles for Precise Selection in Translational Medicine.解析间充质干细胞/基质细胞衍生细胞外囊泡的异质性景观,以在转化医学中进行精确选择。
Adv Healthc Mater. 2023 Jun;12(15):e2202453. doi: 10.1002/adhm.202202453. Epub 2023 Mar 26.
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How Do Extracellular Vesicles Play a Key Role in the Maintenance of Bone Homeostasis and Regeneration? A Comprehensive Review of Literature.
细胞外囊泡在维持骨稳态和再生中如何发挥关键作用?文献综述。
Int J Nanomedicine. 2022 Nov 17;17:5375-5389. doi: 10.2147/IJN.S377598. eCollection 2022.
4
Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption.Runx2 和 Nell-1 在牙囊祖细胞中调节骨重塑和牙齿萌出。
Stem Cell Res Ther. 2022 Sep 30;13(1):486. doi: 10.1186/s13287-022-03140-3.
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Primary failure of tooth eruption: Etiology and management.牙齿萌出原发性失败:病因与处理
Jpn Dent Sci Rev. 2022 Nov;58:258-267. doi: 10.1016/j.jdsr.2022.08.002. Epub 2022 Sep 15.
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Deficiency Promotes Osteoclastogenesis and Exacerbates Periodontitis.缺乏会促进破骨细胞形成并加重牙周炎。
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Extracellular Vesicles in Bone Homeostasis: Emerging Mediators of Osteoimmune Interactions and Promising Therapeutic Targets.细胞外囊泡在骨稳态中的作用:骨免疫相互作用的新兴介质和有前途的治疗靶点。
Int J Biol Sci. 2022 Jun 21;18(10):4088-4100. doi: 10.7150/ijbs.69816. eCollection 2022.
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Nat Commun. 2022 Jul 7;13(1):3919. doi: 10.1038/s41467-022-31646-0.
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