由外泌体介导的牙髓再生相关信号通路研究进展

doi:10.13591/j.cnki.kqyx.2024.10.010

Abstract

Abstract:

Exosomes are a kind of extracellular vesicles, which directly stimulate target cells through receptor-mediated interaction, or exert their biological functions by transferring various bioactive molecules to target cells, playing a key role in intercellular communication between cells and their microenvironment. From the perspective of tissue engineering, pulp regeneration refers to the combination of scaffolds, stem cells, and signaling factors implanted into a properly treated pulp cavity. Under the action of scaffolds and signaling factors, stem cells proliferate and differentiate to form pulp dentin-like complexes, restoring pulp function. In recent years, studies have found that p38MAPK, TGF-β/SMAD, Wnt/β-Catenin signaling pathway and some other signaling pathways are important for the secretion in regulating pulp regeneration, and play a key role in pulp regeneration. Therefore, this article reviews the mechanism and research progress of signaling pathways related to the regulation of pulp regeneration by exosomes.

Key words: exosomes, pulp regeneration, signaling pathway, angiogenesi

CLC Number:

R781.3

CHEN Zirong, TU Hua, CHEN Leyi, XU Wen’an. Advances in signal pathways related to pulp regeneration mediated by exosomes[J]. Stomatology, 2024, 44(10): 775-779.

Figures/Tables 1

References 40

[1]	Yang JW, Yuan GH, Chen Z. Pulp regeneration: Current approaches and future challenges[J]. Front Physiol, 2016, 7: 58. doi: 10.3389/fphys.2016.00058 pmid: 27014076
[2]	刘金凤, 牛雪微, 超博, 等. 牙髓再生的研究现状[J]. 口腔医学研究, 2017, 33(1): 108-111. doi: 10.13701/j.cnki.kqyxyj.2017.01.026
[3]	肖博林, 张伟, 陈刚. 细胞外囊泡与口腔肿瘤免疫[J]. 口腔医学, 2023, 43(9): 769-774.
[4]	石维薇, 郭淑娟. 外泌体在口腔组织发育和再生研究新进展[J]. 口腔医学研究, 2019, 35(11): 1016-1019. doi: 10.13701/j.cnki.kqyxyj.2019.11.002
[5]	Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor[J]. Cell, 1983, 33(3): 967-978. doi: 10.1016/0092-8674(83)90040-5 pmid: 6307529
[6]	Ramachandran S, Palanisamy V. Horizontal transfer of RNAs: Exosomes as mediators of intercellular communication[J]. Wiley Interdiscip Rev RNA, 2012, 3(2): 286-293.
[7]	Yu B, Zhang XM, Li XR. Exosomes derived from mesenchymal stem cells[J]. Int J Mol Sci, 2014, 15(3): 4142-4157. doi: 10.3390/ijms15034142 pmid: 24608926
[8]	Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver[J]. Nat Cell Biol, 2015, 17(6): 816-826. doi: 10.1038/ncb3169 pmid: 25985394
[9]	Syn NL, Wang LZ, Chow EKH, et al. Exosomes in cancer nanomedicine and immunotherapy: Prospects and challenges[J]. Trends Biotechnol, 2017, 35(7): 665-676. doi: S0167-7799(17)30040-9 pmid: 28365132
[10]	何泓志, 麻丹丹. 牙髓干细胞外泌体的研究进展[J]. 口腔疾病防治, 2019, 27(10):652-657. doi: 10.12016/j.issn.2096-1456.2019.09.008
[11]	Martínez-Limón A, Joaquin M, Caballero M, et al. The p38 pathway: From biology to cancer therapy[J]. Int J Mol Sci, 2020, 21(6): 1913.
[12]	Yu D, Zhao X, Cheng JZ, et al. Downregulated microRNA-488 enhances odontoblast differentiation of human dental pulp stem cells via activation of the p38 MAPK signaling pathway[J]. J Cell Physiol, 2019, 234(2): 1442-1451.
[13]	Wang BL, Wang Z, Nan X, et al. Downregulation of microRNA-143-5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen-activated protein kinases 14-dependent p38 mitogen-activated protein kinases signaling pathway[J]. J Cell Physiol, 2019, 234(4): 4840-4850.
[14]	Xian XH, Gong QM, Li C, et al. Exosomes with highly angiogenic potential for possible use in pulp regeneration[J]. J Endod, 2018, 44(5): 751-758. doi: S0099-2399(18)30005-0 pmid: 29426641
[15]	Alcayaga-Miranda F, Varas-Godoy M, Khoury M. Harnessing the angiogenic potential of stem cell-derived exosomes for vascular regeneration[J]. Stem Cells Int, 2016, 2016: 3409169.
[16]	Huang CC, Narayanan R, Alapati S, et al. Exosomes as biomimetic tools for stem cell differentiation: Applications in dental pulp tissue regeneration[J]. Biomaterials, 2016, 111: 103-115.
[17]	Zhou ZY, Zheng JM, Lin DL, et al. Exosomes derived from dental pulp stem cells accelerate cutaneous wound healing by enhancing angiogenesis via the Cdc42/p38 MAPK pathway[J]. Int J Mol Med, 2022, 50(6): 143.
[18]	乔虎军, 王国祥, 郝鑫. 转化生长因子β/Smad信号通路和骨关节炎研究进展[J]. 中国运动医学杂志, 2019, 38(2): 143-151.
[19]	Wu ML, Liu XM, Li ZH, et al. SHED aggregate exosomes shuttled miR-26a promote angiogenesis in pulp regeneration via TGF-β/SMAD2/3 signalling[J]. Cell Prolif, 2021, 54(7): e13074.
[20]	杨正涛, 林方梁, 温利梅. miR-508-3p靶向AFF4/TGFβ1信号通路调控人牙髓细胞分化的机制研究[J]. 广西医科大学学报, 2021, 38(9): 1671-1677.
[21]	Hu XL, Zhong YQ, Kong YY, et al. Lineage-specific exosomes promote the odontogenic differentiation of human dental pulp stem cells(DPSCs) through TGFβ1/smads signaling pathway via transfer of microRNAs[J]. Stem Cell Res Ther, 2019, 10(1): 170.
[22]	Chen DF, Wang KW, Zheng Y, et al. Exosomes-mediated LncRNA ZEB1-AS1 facilitates cell injuries by miR-590-5p/ETS1 axis through the TGF-β/smad pathway in oxidized low-density lipoprotein-induced human umbilical vein endothelial cells[J]. J Cardiovasc Pharmacol, 2021, 77(4): 480-490. doi: 10.1097/FJC.0000000000000974 pmid: 33818551
[23]	Yao Y, Chen R, Wang GW, et al. Exosomes derived from mesenchymal stem cells reverse EMT via TGF-β1/Smad pathway and promote repair of damaged endometrium[J]. Stem Cell Res Ther, 2019, 10(1): 225.
[24]	Wang ZT, Tian T, Chen LY, et al. 980 nm photobiomodulation promotes osteo/odontogenic differentiation of the stem cells from human exfoliated deciduous teeth via the cross talk between BMP/smad and Wnt/β-catenin signaling pathways[J]. Photochem Photobiol, 2022, 99(4):1181-1192.
[25]	Zhou Y, Xu J, Luo H, et al. Wnt signaling pathway in cancer immunotherapy[J]. Cancer Lett, 2022, 525:84-96.
[26]	Hunter DJ, Bardet C, Mouraret S, et al. Wnt acts as a prosurvival signal to enhance dentin regeneration[J]. J Bone Miner Res, 2015, 30(7): 1150-1159. doi: 10.1002/jbmr.2444 pmid: 25556760
[27]	Kornsuthisopon C, Photichailert S, Nowwarote N, et al. Wnt signaling in dental pulp homeostasis and dentin regeneration[J]. Arch Oral Biol, 2022, 134: 105322.
[28]	Wang MH, Li J, Ye YY, et al. SHED-derived conditioned exosomes enhance the osteogenic differentiation of PDLSCs via Wnt and BMP signaling in vitro[J]. Differentiation, 2020, 111: 1-11.
[29]	Zhang SC, Yang Y, Jia SX, et al. Exosome-like vesicles derived from Hertwig’s epithelial root sheath cells promote the regeneration of dentin-pulp tissue[J]. Theranostics, 2020, 10(13): 5914-5931.
[30]	Sun JY, Wang ZG, Liu P, et al. Exosomes derived from human gingival mesenchymal stem cells attenuate the inflammatory response in periodontal ligament stem cells[J]. Front Chem, 2022, 10: 863364.
[31]	Yang SD, Guo S, Tong S, et al. Exosomal miR-130a-3p regulates osteogenic differentiation of Human Adipose-Derived stem cells through mediating SIRT7/Wnt/β-catenin axis[J]. Cell Prolif, 2020, 53(10): e12890.
[32]	柴盈, 刘芷扬, 刘玥旻, 等. 人牙髓干细胞来源外泌体促进周围神经损伤修复的实验研究[J]. 中国口腔颌面外科杂志, 2022, 20(2): 105-110.
[33]	Huang GT, Hu M, Lu DH, et al. Protective effect and potential mechanism of Schwann cell-derived exosomes on mechanical damage of rat dorsal root ganglion cells[J]. J Obstet Gynaecol Res, 2021, 47(10): 3691-3701.
[34]	Garrouste F, Remacle-Bonnet M, Fauriat C, et al. Prevention of cytokine-induced apoptosis by insulin-like growth factor-I is independent of cell adhesion molecules in HT29-D4 colon carcinoma cells-evidence for a NF-kappaB-dependent survival mechanism[J]. Cell Death Differ, 2002, 9(7): 768-779. doi: 10.1038/sj.cdd.4401022 pmid: 12058282
[35]	Geng T, Song ZY, Xing JX, et al. Exosome derived from coronary serum of patients with myocardial infarction promotes angiogenesis through the miRNA-143/IGF-IR pathway[J]. Int J Nanomedicine, 2020, 15: 2647-2658.
[36]	Liu Y, Gao Y, Zhan XL, et al. TLR4 activation by lipopolysaccharide and Streptococcus mutans induces differential regulation of proliferation and migration in human dental pulp stem cells[J]. J Endod, 2014, 40(9): 1375-1381.
[37]	Li L, Ge JP. Exosome-derived lncRNA-Ankrd26 promotes dental pulp restoration by regulating miR-150-TLR4 signaling[J]. Mol Med Rep, 2022, 25(5): 152.
[38]	Sun DG, Xin BC, Wu D, et al. miR-140-5p-mediated regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pathway[J]. Eur J Oral Sci, 2017, 125(6): 419-425. doi: 10.1111/eos.12384 pmid: 29130547
[39]	张玲莉, 周绪昌, 吴伟. BMP-Smad信号通路在骨髓间充质干细胞分化中的作用[J]. 中华骨质疏松和骨矿盐疾病杂志, 2019, 12(6): 618-626.
[40]	Fan JB, Lee CS, Kim S, et al. Generation of small RNA-modulated exosome mimetics for bone regeneration[J]. ACS Nano, 2020, 14(9): 11973-11984. doi: 10.1021/acsnano.0c05122 pmid: 32897692

信号通路	发表时间	外泌体来源细胞	靶细胞	效应	文献
p38MAPK	2018年	树突状细胞	HUVECs	促进血管再生,或可用于牙髓再生	[14]
	2016年	DPSCs	DPSCs	促进牙髓样组织再生	[16]
	2022年	DPSCs	HUVECs	促进血管再生,或可用于牙髓再生	[17]
TGF-β/Smad	2021年	SHED	SHED、HUVECs	促进血管再生,或可用于牙髓再生	[19]
	2019年	DPSCs	DPSCs	促进牙源性分化	[21]
Wnt/β-catenin	2020年	SHED	PDLSCs	促进成骨分化,或可用于牙髓牙本质复合体再生	[28]
	2020年	HERS	DPCs	诱导牙髓牙本质样复合体再生	[29]
	2020年	ADSCs	ADSCs	促进成骨分化,或可用于牙髓牙本质复合体再生	[31]

Advances in signal pathways related to pulp regeneration mediated by exosomes

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