AccScience Publishing / GPD / Volume 1 / Issue 2 / DOI: 10.36922/gpd.v1i2.99
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Exosomes: A bridge of periodontitis and systemic diseases

Jing Xu1,2† Xin Chang1,2† Huixin Zhang1,2 Mengying Si1,2 Huiying Su1,2 Lilan Cao1,2 Yingying Li3 Yuankun Zhai1,2,4*
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1 Department of Oral Biology, School of Stomatology, Henan University, Kaifeng, Henan, 475000, China
2 Kaifeng Key Laboratory of Periodontal Tissue Engineering, Kaifeng, Henan, 475000, China
3 Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province), Zhengzhou, Henan, 450000, China
4 Henan International Joint Laboratory for Nuclear Protein Regulation, Kaifeng, Henan, 475000, China
Submitted: 17 May 2022 | Accepted: 12 July 2022 | Published: 4 August 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Periodontitis, a common oral disease, is featured with complex etiology, progressive and prognosis varies according to the severity of periodontitis. Exosomes belong a kind of cystic vesicles with biological activity, which widely exist in human body fluids. Exosomes play an irreparable role in signal transmission and material exchange between cells, maintaining cell functions, and regulating body immunity and homeostasis. Exosomes are closely related to periodontitis, and recent study of exosomes has provided new directions and ideas for the diagnosis and treatment of periodontitis. Similarly, as extracellular vesicles, exosomes play a bridging role between periodontitis and some systemic diseases. In this process, exosomes participate in and regulate the process of systemic diseases by carrying nucleic acids, proteins, lipids, etc., and exhibit different bioactive effects according to the different substances carried in exosomes. In this paper, we summarize the latest research progress of exosomes, especially in the periodontitis and some systemic diseases, and review the potential value of exosomes in periodontitis diagnosis and treatments.

Keywords
Periodontitis
Exosomes
Periodontal regeneration
Osteoporosis
Kidney disease
Funding
Foundation of Science & Technology Department of Henan Province, China
Natural Science Foundation of Education Department of Henan Province, China
Foundation of National Health Commission of Henan Province, China
Foundation of Science & Technology Department of Luoyang City, Henan Province, China
Conflict of interest
None.
References
[1]

Song B, Zhang YL, Chen LJ, et al., 2017, The role of toll-like receptors in periodontitis. Oral Dis, 23(2): 168–180.

[2]

Hoare A, Soto C, Rojas-Celis V, et al., 2019, Chronic inflammation as a link between periodontitis and carcinogenesis. Mediators Inflamm, 2019: 1029857. https://doi.org/10.1155/2019/1029857 

[3]

Lundmark A, Hu YO, Huss M, et al., 2019, Identification of salivary microbiota and its association with host inflammatory mediators in periodontitis. Front Cell Infect Microbiol, 9: 216. https://doi.org/10.3389/fcimb.2019.00216

[4]

Shi T, Jin Y, Miao Y, et al., 2020, IL-10 secreting B cells regulate periodontal immune response during periodontitis. Odontology, 108(3): 350–357. https://doi.org/10.1007/s10266-019-00470-2

[5]

Xu S, Zhang G, Guo JF, et al., 2021, Associations between osteoporosis and risk of periodontitis: A pooled analysis of observational studies. Oral Dis, 27(2): 357–369. https://doi.org/10.1111/odi.13531

[6]

Wang CJ, McCauley LK, 2016, Osteoporosis and periodontitis. Curr Osteoporos Rep, 14(6): 284–291. https://doi.org/10.1007/s11914-016-0330-3

[7]

Serni L, Caroti L, Barbato L, et al., 2021, Association between chronic kidney disease and periodontitis. A systematic review and metanalysis. Oral Dis, 2021: 14062. https://doi.org/10.1111/odi.14062

[8]

Parsegian K, Randall D, Curtis M, et al., 2022, Association between periodontitis and chronic kidney disease. Periodontol 2000, 89(1): 114–124. https://doi.org/10.1111/prd.12431

[9]

Liccardo D, Marzano F, Carraturo F, et al., 2020, Potential bidirectional relationship between periodontitis and Alzheimer’s disease. Front Physiol, 11: 683. https://doi.org/10.3389/fphys.2020.00683

[10]

Werber T, Bata Z, Vaszine ES, et al., 2021, The association of periodontitis and Alzheimer’s disease: How to hit two birds with one stone. J Alzheimers Dis, 84(1): 1–21. https://doi.org/10.3233/jad-210491

[11]

Leira Y, Seoane J, Blanco M, et al., 2017, Association between periodontitis and ischemic stroke: A systematic review and meta-analysis. Eur J Epidemiol, 32(1): 43–53. https://doi.org/10.1007/s10654-016-0170-6

[12]

Bengtsson VW, Persson GR, Berglund JS, et al., 2021, Periodontitis related to cardiovascular events and mortality: A long-time longitudinal study. Clin Oral Investig, 25(6): 4085–4095. https://doi.org/10.1007/s00784-020-03739-x

[13]

Sanz M, Del Castillo AM, Jepsen S, et al., 2020, Periodontitis and cardiovascular diseases. Consensus report. Global Heart, 15(1): 1.

[14]

Cardoso EM, Reis C, Manzanares-Céspedes MC, 2018, Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med, 130(1): 98–104. https://doi.org/10.1080/00325481.2018.1396876 

[15]

Szatanek R, Baj-Krzyworzeka M, Zimoch J, et al., 2017, Methods of choice for extracellular vesicles (EVs) characterization. Int J Mol Sci, 18(6): 1153. https://doi.org/10.3390/ijms18061153

[16]

Meldolesi J, 2018, Exosomes and ectosomes in intercellular communication. Curr Biol, 28(8): R435–R444. https://doi.org/10.1016/j.cub.2018.01.059 

[17]

Latifkar A, Hur YH, Sanchez JC, et al., 2019, New insights into extracellular vesicle biogenesis and function. J Cell Sci, 132(13): jcs222406. https://doi.org/10.1242/jcs.222406

[18]

Console L, Scalise M, Indiveri C, 2019, Exosomes in inflammation and role as biomarkers. Clin Chim Acta, 488: 165–171. https://doi.org/10.1016/j.cca.2018.11.009

[19]

Chen BY, Sung CW, Chen C, et al., 2019, Advances in exosomes technology. Clin Chim Acta, 493: 14–19.

[20]

Peng Q, Yang JY, Zhou G, 2020, Emerging functions and clinical applications of exosomes in human oral diseases.  Cell Biosci, 10: 68. https://doi.org/10.1186/s13578-020-00424-0

[21]

Nakao Y, Fukuda T, Zhang Q, et al., Exosomes from TNF- α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater, 122: 306–324. https://doi.org/10.1016/j.actbio.2020.12.046

[22]

Li D, Wang Y, Jin X, et al., 2020, NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice. J Neuroinflammation, 17(1): 126. https://doi.org/10.1186/s12974-020-01787-4

[23]

Fotuhi SN, Khalaj-Kondori M, Feizi MA, et al., 2019, Long non-coding RNA BACE1-as may serve as an Alzheimer’s disease blood-based biomarker. J Mol Neurosci, 69(3): 351–359. https://doi.org/10.1007/s12031-019-01364-2

[24]

Hadavand M, Hasni S, 2019, Exosomal biomarkers in oral diseases. Oral Dis, 25(1): 10–15. https://doi.org/10.1111/odi.12878 

[25]

Croitoru IC, CrăiŢoiu Ş, Petcu CM, et al., 2016, Clinical, imagistic and histopathological study of chronic apical periodontitis. Rom J Morphol Embryol, 57(2 Suppl): 719–728.

[26]

Kinane DF, Stathopoulou PG, Papapanou PN, 2017, Periodontal diseases. Nat Rev Dis Primers, 3: 17038. https://doi.org/10.1038/nrdp.2017.38

[27]

Murakami S, Mealey BL, Mariotti A, et al., 2018, Dental plaque-induced gingival conditions. J Periodontol, 89(Suppl 1):S17–S27. https://doi.org/10.1002/jper.17-0095

[28]

Bui FQ, Almeida-da-Silva CL, Huynh B, et al., 2019, Association between periodontal pathogens and systemic disease. Biomed J, 42(1): 27–35. https://doi.org/10.1016/j.bj.2018.12.001

[29]

Dosseva-Panova VT, Popova CL, Panov VE, 2014, Subgingival microbial profile and production of proinflammatory cytokines in chronic periodontitis. Folia Med (Plovdiv), 56(3): 152–160. https://doi.org/10.2478/folmed-2014-0022

[30]

Mysak J, Podzimek S, Sommerova P, et al., 2014, Porphyromonas gingivalis: Major periodontopathic pathogen overview. J Immunol Res, 2014: 476068. https://doi.org/10.1155/2014/476068

[31]

Kulkarni PG, Gosavi S, Haricharan PB, et al., 2018, Molecular detection of Porphyromonas gingivalis in chronic periodontitis patients. J Contemp Dent Pract, 19(8): 992–996. https://doi.org/10.5005/jp-journals-10024-2371

[32]

Benakanakere M, Kinane DF, 2012, Innate cellular responses to the periodontal biofilm. Front Oral Biol, 15: 41–55. https://doi.org/10.1159/000329670

[33]

Silva LM, Brenchley L, Moutsopoulos NM, 2109, Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis. Immunol Rev, 287(1): 226–235. https://doi.org/10.1111/imr.12724

[34]

Pan W, Wang Q, Chen Q, 2019, The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci, 11(3): 30. https://doi.org/10.1038/s41368-019-0064-z

[35]

Huang Y, Tang X, 2017, Research progress on the relationship between monocytes phagocyte system and periodontitis. Int J Stomatol, 44(5): 528–532.

[36]

Germic N, Frangez Z, Yousefi S, et al., 2019, Regulation of the innate immune system by autophagy: Monocytes, macrophages, dendritic cells and antigen presentation. Cell Death Differ, 26(4): 715–727. https://doi.org/10.1038/s41418-019-0297-6

[37]

Pioli PD, 2019, Plasma cells, the next generation: Beyond antibody secretion. Front Immunol, 10: 2768. https://doi.org/10.3389/fimmu.2019.02768 

[38]

Gadekar NB, Hosmani JV, Bhat KG, et al., 2018, Detection of antibodies against Aggregatibacter actinomycetemcomitans in serum and saliva through ELISA in periodontally healthy individuals and individuals with chronic periodontitis. Microb Pathog, 125: 438–442. https://doi.org/10.1016/j.micpath.2018.10.007

[39]

Weis-Garcia F, Carnahan RH, 2017, Characterizing antibodies. Cold Spring Harbor Protoc, 2017(11): pdb.top093823. https://doi.org/10.1101/pdb.top093823

[40]

Sheethal HS, Kn H, Smitha T, et al., 2018, Role of mast cells in inflammatory and reactive pathologies of pulp, periapical area and periodontium. J Oral Maxillofac Pathol, 22(1): 92–7.

[41]

Silva N, Abusleme L, Bravo D, et al., 2015, Host response mechanisms in periodontal diseases. J Appl Oral Sci, 23(3): 329–355. https://doi.org/10.1590/1678-775720140259

[42]

Garlet GP, 2010, Destructive and protective roles of cytokines in periodontitis: A re-appraisal from host defense and tissue destruction viewpoints. J Dent Res, 89(12): 1349–1363. https://doi.org/10.1177/0022034510376402 

[43]

Li J, Casanova JL, Puel A, 2018, Mucocutaneous IL-17 immunity in mice and humans: Host defense vs. excessive inflammation. Mucosal Immunol, 11(3): 581–589. https://doi.org/10.1038/mi.2017.97

[44]

Abdulkhaleq LA, Assi MA, Abdullah R, et al., 2018, The crucial roles of inflammatory mediators in inflammation: A review. Vet World, 11(5): 627–635. https://doi.org/10.14202/vetworld.2018.627-635

[45]

Arbab M, Tahir S, Niazi MK, et al., 2017, TNF-α genetic predisposition and higher expression of inflammatory pathway components in keratoconus. Invest Ophthalmol Vis Sci, 58(9): 3481–3487. https://doi.org/10.1167/iovs.16-21400

[46]

Majumder P, Thou K, Bhattacharya M, et al., 2018, Association of tumor necrosis factor-α (TNF-α) gene promoter polymorphisms with aggressive and chronic periodontitis in the Eastern Indian population. Biosci Rep, 38(4): BSR20171212. https://doi.org/10.1042/bsr20171212

[47]

Seutter S, Winfield J, Esbitt A, et al., 2020, Interleukin 1β and prostaglandin E2 affect expression of DNA methylating and demethylating enzymes in human gingival fibroblasts. Int immunopharmacol, 78: 105920. https://doi.org/10.1016/j.intimp.2019.105920

[48]

Grga D, Dzeletović B, Damjanov M, et al., 2013, Prostaglandin E2 in apical tissue fluid and postoperative pain in intact and teeth with large restorations in two endodontic treatment visits. Srp Arh Celok Lek, 141(1–2): 17–21. https://doi.org/10.2298/sarh1302017g

[49]

Offenbacher S, Heasman PA, Collins JG, 1993, Modulation of host PGE2 secretion as a determinant of periodontal disease expression. J Periodontol, 64(5 Suppl): 432–444. https://doi.org/10.1902/jop.1993.64.5.432

[50]

Oduncuoglu BF, Kayar NA, Haliloglu S, et al, 2018, Effects of a cyclic NSAID regimen on levels of gingival crevicular fluid prostaglandin E(2)and Interleukin-1β: A 6-month randomized controlled clinical trial. Niger J Clin Pract, 21(5): 658–666. https://doi.org/10.4103/njcp.njcp_221_17 

[51]

Cox SW, Eley BM, Kiili M, et al., 2006, Collagen degradation by interleukin-1beta-stimulated gingival fibroblasts is accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases. Oral Dis, 12(1): 34–40. https://doi.org/10.1111/j.1601-0825.2005.01153.x

[52]

Álvares PR, Arruda JA, Silva LP, et al., 2017, Immunohistochemical expression of TGF-β1 and MMP-9 in periapical lesions. Braz Oral Res, 31: e51. https://doi.org/10.1590/1807-3107bor-2017.vol31.0051

[53]

Cocucci E, Meldolesi J, 2015, Ectosomes and exosomes: Shedding the confusion between extracellular vesicles. Trends Cell Biol, 25(6): 364–372. https://doi.org/10.1016/j.tcb.2015.01.004

[54]

Doyle LM, Wang MZ, 2019, Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells, 8(7): 727. https://doi.org/10.3390/cells8070727

[55]

Mashouri L, Yousefi H, Aref AR, et al., 2019, Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer, 18(1): 75. https://doi.org/10.1186/s12943-019-0991-5

[56]

Mathivanan S, Ji H, Simpson RJ, 2010, Exosomes: Extracellular organelles important in intercellular communication. J Proteom, 73(10): 1907–1920. https://doi.org/10.1016/j.jprot.2010.06.006

[57]

Kalluri R, LeBleu VS, 2020, The biology, function, and biomedical applications of exosomes. Science, 367(6478): eaau6977. https://doi.org/10.1126/science.aau6977

[58]

Emanueli C, Shearn AI, Angelini GD, et al., 2015, Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascul Pharmacol, 71: 24–30. https://doi.org/10.1016/j.vph.2015.02.008

[59]

Cai J, Wu J, Wang J, et al., 2020, Extracellular vesicles derived from different sources of mesenchymal stem cells: Therapeutic effects and translational potential. Cell Biosci, 10: 69. https://doi.org/10.1186/s13578-020-00427-x

[60]

Liang B, He X, Zhao YX, et al., 2020, Advances in exosomes derived from different cell sources and cardiovascular diseases. Biomed Res Int, 2020: 7298687. https://doi.org/10.1155/2020/7298687

[61]

Gurunathan S, Kang MH, Jeyaraj M, et al., 2019, Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells, 8(4): 307. https://doi.org/10.3390/cells10020462

[62]

Xunian Z, Kalluri R, 2020, Biology and therapeutic potential of mesenchymal stem cell-derived exosomes. Cancer Sci, 111(9): 3100–3110. https://doi.org/10.1111/cas.14563

[63]

Milane L, Singh A, Mattheolabakis G, et al., 2015, Exosome mediated communication within the tumor microenvironment. J Control Release, 219: 278–294. https://doi.org/10.1016/j.jconrel.2015.06.029

[64]

Yáñez-Mó M, Siljander PR, Andreu Z, et al., 2015, Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 4: 27066.

[65]

van Niel GV, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol, 19: 213–228. https://doi.org/10.1038/nrm.2017.125

[66]

Record M, Silvente-Poirot S, Poirot M, et al., 2018, Extracellular vesicles: Lipids as key components of their biogenesis and functions. J Lipid Res, 59(8): 1316–1324. https://doi.org/10.1194/jlr.e086173

[67]

Phuyal S, Hessvik NP, Skotland T, et al., 2014, Regulation of exosome release by glycosphingolipids and flotillins. FEBS J, 281(9): 2214–2227. https://doi.org/10.1111/febs.12775

[68]

Raposo G, Stoorvogel W, 2013, Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol, 200(4): 373–383. https://doi.org/10.1083/jcb.201211138

[69]

Zhang Y, Liu Y, Liu H, et al., 2019, Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci, 9: 19. https://doi.org/10.1186/s13578-019-0282-2

[70]

Deng H, Sun C, Sun Y, et al., 2018, Lipid, protein, and MicroRNA composition within mesenchymal stem cell-derived exosomes. Cell Reprogram, 20(3): 178–186. https://doi.org/10.1089/cell.2017.0047

[71]

Barile L, Vassalli G, 2017, Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther, 174: 63–78. https://doi.org/10.1016/j.pharmthera.2017.02.020

[72]

Crescitelli R, Lässer C, Szabó TG, et al., 2013, Distinct RNA profiles in subpopulations of extracellular vesicles: Apoptotic bodies, microvesicles and exosomes. J Extracell Vesicles, 12: 2. https://doi.org/10.3402/jev.v2i0.20677

[73]

Zhang J, Li S, Li L, et al., 2015, Exosome and exosomal microRNA: Trafficking, sorting, and function. Genom Proteom Bioinform, 13(1): 17–24. https://doi.org/10.1016/j.gpb.2015.02.001

[74]

Fabbri M, Paone A, Calore F, et al., 2012, MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A, 109(31): E2110–E2116. https://doi.org/10.1073/pnas.1209414109

[75]

Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, et al., 2016, Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. Elife. 5: e19276. https://doi.org/10.1101/040238

[76]

Samanta S, Rajasingh S, Drosos N, et al., 2018, Exosomes: New molecular targets of diseases. Acta Pharmacol Sin, 39(4): 501–513. https://doi.org/10.1038/aps.2017.162 

[77]

Zhang L, Yu D, 2019, Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer, 1871(2): 455–468.

[78]

Lane RE, Korbie D, Trau M, et al., 2017, Purification protocols for extracellular vesicles. Methods Mol Biol (Clifton, NJ), 1660: 111–130. https://doi.org/10.1007/978-1-4939-7253-1_10

[79]

Momen-Heravi F, 2017, Isolation of extracellular vesicles by ultracentrifugation. Methods Mol Biol (Clifton, NJ). 1660: 25–32. https://doi.org/10.1007/978-1-4939-7253-1_3

[80]

Cao F, Gao Y, Chu Q, et al., 2019, Proteomics comparison of exosomes from serum and plasma between ultracentrifugation and polymer-based precipitation kit methods. Electrophoresis, 40(23–24): 3092–3098. https://doi.org/10.1002/elps.201900295

[81]

Zhang Z, Wang C, Li T, et al., 2014, Comparison of ultracentrifugation and density gradient separation methods for isolating Tca8113 human tongue cancer cell line-derived exosomes. Oncol Lett, 8(4): 1701–1706. https://doi.org/10.3892/ol.2014.2373

[82]

He L, Zhu D, Wang J, et al., 2019, A highly efficient method for isolating urinary exosomes. Int J Mol Med, 43(1): 83–90.

[83]

Li M, Lou D, Chen J, et al., 2021, Deep dive on the proteome of salivary extracellular vesicles: Comparison between ultracentrifugation and polymer-based precipitation isolation. Anal Bioanal Chem, 413(2): 365–375. https://doi.org/10.1007/s00216-020-03004-w 

[84]

Greening DW, Xu R, Ji H, et al., 2015, A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. Methods Mol Biol (Clifton, NJ), 1295: 179–209. https://doi.org/10.1007/978-1-4939-2550-6_15

[85]

Chiricosta L, Silvestro S, Gugliandolo A, et al., 2020, Extracellular vesicles of human periodontal ligament stem cells contain MicroRNAs associated to proto-oncogenes: Implications in cytokinesis. Front Genet, 11: 582. https://doi.org/10.3389/fgene.2020.00582

[86]

Fernández A, Cárdenas AM, Astorga J, et al., 2019, Expression of toll-like receptors 2 and 4 and its association with matrix metalloproteinases in symptomatic and asymptomatic apical periodontitis. Clin Oral Investig, 23(12): 4205–4212. https://doi.org/10.1007/s00784-019-02861-9

[87]

Choi JW, Kim SC, Hong SH, et al., 2017, Secretable small RNAs via outer membrane vesicles in periodontal pathogens. J Dent Res, 96(4): 458–616. https://doi.org/10.1177/0022034516685071

[88]

Cafferata EA, Castro-Saavedra S, Fuentes-Barros G, et al., 2021, Boldine inhibits the alveolar bone resorption during ligature-induced periodontitis by modulating the Th17/Treg imbalance. J Periodontol, 92(1): 123–136. https://doi.org/10.1002/jper.20-0055

[89]

Zheng Y, Dong C, Yang J, et al., 2109, Exosomal microRNA- 155-5p from PDLSCs regulated Th17/Treg balance by targeting sirtuin-1 in chronic periodontitis. J Cell Physiol, 234(11): 20662–20674. https://doi.org/10.1002/jcp.28671 

[90]

Herbert BA, Novince CM, Kirkwood KL, 2016, Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis. Mol Oral Microbiol, 31(3): 207–227. https://doi.org/10.1111/omi.12119

[91]

Han EC, Choi SY, Lee Y, et al., 2019, Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-α production in human macrophages and cross the blood-brain barrier in mice. FASEB J, 33(12): 13412–13422. https://doi.org/10.1096/fj.201901575r

[92]

Yu J, Lin Y, Xiong X, et al., 2019, Detection of exosomal PD-L1 RNA in saliva of patients with periodontitis. Front Genet, 10: 202. https://doi.org/10.3389/fgene.2019.00202

[93]

Huang X, Hu X, Zhao M, et al., 2020, Analysis of salivary exosomal proteins in young adults with severe periodontitis. Oral Dis, 26(1): 173–181. https://doi.org/10.1111/odi.13217

[94]

Brosseau C, Colas L, Magnan A, et al., 2018, CD9 tetraspanin: A new pathway for the regulation of inflammation? Front Immunol, 9: 2316. https://doi.org/10.3389/fimmu.2018.02316

[95]

Zhao LR, Mao JQ, Zhao BJ, et al., 2019, Isolation and biological characteristics of exosomes derived from periodontal ligament stem cells. Shanghai Kou Qiang Yi Xue, 28(4): 343–348.

[96]

Zhao M, Dai W, Wang H, et al., 2019, Periodontal ligament fibroblasts regulate osteoblasts by exosome secretion induced by inflammatory stimuli. Arch Oral Biol, 105: 27–34. https://doi.org/10.1016/j.archoralbio.2019.06.002

[97]

Papadopoulos G, Kramer CD, Slocum CS, et al., 2014, A mouse model for pathogen-induced chronic inflammation at local and systemic sites. J Vis Exp, 90: e51556. https://doi.org/10.3791/51556

[98]

Wang M, Li J, Ye Y, et al., 2020, SHED-derived conditioned exosomes enhance the osteogenic differentiation of PDLSCs via Wnt and BMP signaling in vitro. Differentiation, 111: 1–11. https://doi.org/10.1016/j.diff.2019.10.003

[99]

Straka M, Straka-Trapezanlidis M, Deglovic J, et al., 2015, Periodontitis and osteoporosis. Neuroendocrinol Lett, 36(5): 401–406.

[100]

Abdi K, Chen T, Klein BA, et al., 2017, Mechanisms by which Porphyromonas gingivalis evades innate immunity. PLoS One, 12(8): e0182164. https://doi.org/10.1371/journal.pone.0182164

[101]

Sun W, Zhao C, Li Y, et al., 2016, Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov, 2: 16015. https://doi.org/10.1038/celldisc.2016.15

[102]

Chunhui HU, Yinghua LI, Zhi Q, et al., 2019, Proteomics analysis of serum exosomes and its application in osteoporosis. Chin J Chromatogr, 37(8): 863–871.

[103]

Wang Z, Sun D, 2018, Adipose-derived mesenchymal stem cells: A new tool for the treatment of renal fibrosis. Stem Cells Dev, 27(20): 1406–1411. https://doi.org/10.1089/scd.2017.0304 

[104]

Zhao T, Sun F, Liu J, et al., 2019, Emerging role of mesenchymal stem cell-derived exosomes in regenerative medicine. Curr Stem Cell Res Ther, 14(6): 482–494. https://doi.org/10.2174/1574888x14666190228103230

[105]

Nogueira A, Pires MJ, Oliveira PA, 2017, Pathophysiological mechanisms of renal fibrosis: A review of animal models and therapeutic strategies. In Vivo (Athens, Greece), 31(1): 1–22. https://doi.org/10.21873/invivo.11019

[106]

Meng XM, Inflammatory mediators and renal fibrosis. Adv Exp Med Biol, 1165: 381–406.

[107]

Berchtold L, Friedli I, Vallée JP, et al., 2017, Diagnosis and assessment of renal fibrosis: The state of the art. Swiss Med Wkly, 147: w14442. https://doi.org/10.4414/smw.2017.14442

[108]

Khalaf H, Lönn J, Bengtsson T, 2014, Cytokines and chemokines are differentially expressed in patients with periodontitis: Possible role for TGF-β1 as a marker for disease progression. Cytokine, 67(1): 29–35. https://doi.org/10.1016/j.cyto.2014.02.007

[109]

Meng XM, Nikolic-Paterson DJ, Lan HY, 2016, TGF-β: The master regulator of fibrosis. Nat Rev Nephrol, 12(6): 325–338. https://doi.org/10.1038/nrneph.2016.48

[110]

Ma TT, Meng XM, 2019, TGF-β/smad and renal fibrosis. Adv Exp Med Biol, 1165: 347–364.

[111]

Chen P, Xuan DY, Zhang JC, 2017, Periodontitis aggravates kidney damage in obese mice by MMP2 regulation. Bratisl Lek Listy, 118(12): 740–745. https://doi.org/10.4149/bll_2017_140

[112]

Borges FT, Melo SA, Özdemir BC, et al, 2013, TGF-β1- containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol, 24(3): 385–392.https://doi.org/10.3410/f.717988251.793472538 

[113]

Sonoda H, Lee BR, Park KH, et al., 2019, miRNA profiling of urinary exosomes to assess the progression of acute kidney injury. Sci Rep, 9(1): 4692. https://doi.org/10.1038/s41598-019-40747-8

[114]

Weller J, Budson A, 2018, Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7: F1000 Faculty Rev–1161. https://doi.org/10.12688/f1000research.14506.1

[115]

Herrera-Espejo S, Santos-Zorrozua B, Álvarez-González P, et al., 2019, A systematic review of MicroRNA expression as biomarker of late-onset Alzheimer’s disease. Mol Neurobiol, 56(12): 8376–8391. https://doi.org/10.1007/s12035-019-01676-9

[116]

Singhrao SK, Harding A, Poole S, et al., 2015, Porphyromonas gingivalis periodontal infection and its putative links with Alzheimer’s disease. Mediators Inflam, 2015: 137357. https://doi.org/10.1155/2015/137357 

[117]

Wu Z, Nakanishi H, 2014, Connection between periodontitis and Alzheimer’s disease: Possible roles of microglia and leptomeningeal cells. J Pharmacol Sci, 126(1): 8–13. https://doi.org/10.1254/jphs.14r11cp

[118]

Ide M, Harris M, Stevens A, et al., 2016, Periodontitis and cognitive decline in Alzheimer’s disease. PLoS One, 11(3): e0151081. https://doi.org/10.1371/journal.pone.0151081

[119]

Saman S, Lee NC, Inoyo I, et al., 2014, Proteins recruited to exosomes by tau overexpression implicate novel cellular mechanisms linking tau secretion with Alzheimer’s disease. J Alzheimers Dis, 40(Suppl 1): S47–S70. https://doi.org/10.3233/jad-132135

[120]

Vella LJ, Hill AF, Cheng L, 2016, Focus on extracellular vesicles: Exosomes and their role in protein trafficking and biomarker potential in Alzheimer’s and Parkinson’s disease. Int J Mol Sci, 17(2): 173. https://doi.org/10.3390/ijms17020173

[121]

Trotta T, Panaro MA, Cianciulli A, et al., 2018, Microglia-derived extracellular vesicles in Alzheimer’s disease: A double-edged sword. Biochem Pharmacol, 148: 184–192. https://doi.org/10.1016/j.bcp.2017.12.020

[122]

Li D, Li YP, Li YX, et al., 2018, Effect of regulatory network of exosomes and microRNAs on neurodegenerative diseases. Chin Med J (Engl), 131(18): 2216–2225. https://doi.org/10.4103/0366-6999.240817

[123]

Zheng T, Pu J, Chen Y, et al., 2017, Plasma exosomes spread and cluster around β-amyloid plaques in an animal model of Alzheimer’s disease. Front Aging Neurosci, 9: 12. https://doi.org/10.3389/fnagi.2017.00012

[124]

Isabel C, Calvet D, Mas JL, 2016, Stroke prevention. Presse Med, 45(12 Pt 2): e457-e471. https://doi.org/10.1016/j.lpm.2016.10.009

[125]

Zhang ZG, Chopp M, 2016, Exosomes in stroke pathogenesis and therapy. J Clin Investig, 126(4): 1190–1197.

[126]

Sen S, Giamberardino LD, Moss K, et al., 2018, Periodontal disease, regular dental care use, and incident ischemic stroke. Stroke, 49(2): 355–362. https://doi.org/10.1161/strokeaha.117.018990

[127]

Yousuf O, Mohanty BD, Martin SS, et al., 2013, High-sensitivity C-reactive protein and cardiovascular disease: A resolute belief or an elusive link? J Am Coll Cardiol, 62(5): 397–408.

[128]

Pietiäinen M, Liljestrand JM, Kopra E, et al., 2018, Mediators between oral dysbiosis and cardiovascular diseases. Eur J Oral Sci, 126(Suppl 1): 26–36. https://doi.org/10.1111/eos.12423

[129]

Chen Y, Song Y, Huang J, et al., 2017, Increased circulating exosomal miRNA-223 is associated with acute ischemic stroke. Front Neurol, 8: 57. https://doi.org/10.3389/fneur.2017.00057

[130]

Li DB, Liu JL, Wang W, et al., 2017, Plasma exosomal miR- 422a and miR-125b-2-3p serve as biomarkers for ischemic stroke. Curr Neurovasc Res, 14(4): 330–337. https://doi.org/10.2174/1567202614666171005153434

[131]

Ji Q, Ji Y, Peng J, et al., 2016, Increased brain-specific MiR-9 and MiR-124 in the serum exosomes of acute ischemic stroke patients. PLoS One, 11(9): e0163645. https://doi.org/10.1371/journal.pone.0163645

[132]

Van Camp G, 2014, Cardiovascular disease prevention. Acta Clin Belg, 69: 407–411.

[133]

Khumaedi AI, Purnamasari D, Wijaya IP, et al., 2019, The relationship of diabetes, periodontitis and cardiovascular disease. Diabetes Metab Syndr, 13(2): 1675–1678. https://doi.org/10.1016/j.dsx.2019.03.023

[134]

Mahalakshmi K, Krishnan P, Arumugam SB, 2017, Association of periodontopathic anaerobic bacterial co-occurrence to atherosclerosis a cross-sectional study. Anaerobe, 44: 66–72. https://doi.org/10.1016/j.anaerobe.2017.02.003

[135]

Badimon L, Peña E, Arderiu G, et al., 2018, C-reactive protein in atherothrombosis and angiogenesis. Front Immunol, 9: 430. https://doi.org/10.3389/fimmu.2018.00430

[136]

Chistiakov DA, Orekhov AN, Bobryshev YV, 2015, Extracellular vesicles and atherosclerotic disease. Cell Mol Life Sci, 72(14): 2697–2708. https://doi.org/10.1007/s00018-015-1906-2

[137]

Wang C, Zhang C, Liu L, et al., 2017, Macrophage-derived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury. Mol Ther, 25(1): 192–204. https://doi.org/10.1016/j.ymthe.2016.09.001

[138]

Widera C, Gupta SK, Lorenzen JM, et al., 2011, Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. J Mol Cell Cardiol, 51(5): 872–875. https://doi.org/10.1016/j.yjmcc.2011.07.011

[139]

Atsawasuwan P, Lazari P, Chen Y, et al., 2018, Secretory microRNA-29 expression in gingival crevicular fluid during orthodontic tooth movement. PLoS One, 13(3): e0194238. https://doi.org/10.1371/journal.pone.0194238

[140]

Tomofuji T, Yoneda T, Machida T, et al., 2016, MicroRNAs as serum biomarkers for periodontitis. J Clin Periodontol, 43(5): 418–425. https://doi.org/10.1111/jcpe.12536

[141]

Micó-Martínez P, García-Giménez JL, Seco-Cervera M, et al., 2018, miR-1226 detection in GCF as potential biomarker of chronic periodontitis: A pilot study. Med Oral Patol Oral Cir Bucal, 23(3): e308–e314. https://doi.org/10.4317/medoral.22329

[142]

Shi H, Jiang X, Xu C, et al., 2022, MicroRNAs in serum exosomes as circulating biomarkers for postmenopausal osteoporosis. Front Endocrinol, 13: 819056. https://doi.org/10.3389/fendo.2022.819056

[143]

Sun Y, Kuek V, Liu Y, et al., 2018, MiR-214 is an important regulator of the musculoskeletal metabolism and disease. J Cell Physiol, 234(1): 231–245. https://doi.org/10.1002/jcp.26856

[144]

Lv CY, Ding WJ, Wang YL, et al., 2018, A PEG-based method for the isolation of urinary exosomes and its application in renal fibrosis diagnostics using cargo miR- 29c and miR-21 analysis. Int Urol Nephrol, 50(5): 973–982. https://doi.org/10.1007/s11255-017-1779-4

[145]

Solé C, Cortés-Hernández J, Felip ML, et al., 2015, miR- 29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis. Nephrol Dial Transplant, 30(9): 1488– 1496. https://doi.org/10.1093/ndt/gfv128

[146]

Gudehithlu KP, Hart P, Joshi A, et al., 2019, Urine exosomal ceruloplasmin: A potential early biomarker of underlying kidney disease. Clin Exp Nephrol, 23(8): 1013–1021. https://doi.org/10.1007/s10157-019-01734-5

[147]

Chun-Yan L, Zi-Yi Z, Tian-Lin Y, et al., Liquid biopsy biomarkers of renal interstitial fibrosis based on urinary exosome. Exp Mol Pathol, 2018, 105(2): 223–228. https://doi.org/10.1016/j.yexmp.2018.08.004

[148]

Tan L, Yu JT, Tan MS, et al., 2014, Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer’s disease. J Alzheimers Dis, 40(4): 1017–1027. https://doi.org/10.3233/jad-132144

[149]

Riancho J, Vázquez-Higuera JL, Pozueta A, et al., 2017, MicroRNA profile in patients with Alzheimer’s disease: Analysis of miR-9-5p and miR-598 in raw and exosome enriched cerebrospinal fluid samples. J Alzheimers Dis, 57(2): 483–491. https://doi.org/10.3233/jad-161179

[150]

Zhang M, Han W, Xu Y, et al., 2021, Serum miR-128 serves as a potential diagnostic biomarker for Alzheimer’s disease. Neuropsychiatr Dis Treat, 17: 269–275. https://doi.org/10.2147/ndt.s290925

[151]

Tan L, Yu JT, Liu QY, et al., 2014, Circulating miR-125b as a biomarker of Alzheimer’s disease. J Neurol Sci, 336(1–2): 52–56.

[152]

Sun X, Lv J, Chen D, et al., 2019, Serum miR-599 serves as a biomarker for ischemic stroke patients. Clin Lab, 65(7): 181256. https://doi.org/10.7754/clin.lab.2019.181256

[153]

Liu G, Cao C, Zhu M, 2019, Peripheral blood miR-451 may serve as a biomarker of ischemic stroke. Clin Lab, 65(9): 190309. https://doi.org/10.7754/clin.lab.2019.190309

[154]

Du L, Xu Z, Wang X, et al., 2020, Integrated bioinformatics analysis identifies microRNA-376a-3p as a new microRNA biomarker in patient with coronary artery disease. Am J Transl Res, 12(2): 633–648.

[155]

Lu T, Li X, Long C, et al., 2021, Circulating miR-27b as a biomarker of the development and progression of carotid artery stenosis. Clin Appl Thromb Hemost, 27: 10760296211057903. https://doi.org/10.1177/10760296211057903

[156]

Maciejak A, Kostarska-Srokosz E, Gierlak W, et al., 2018, Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep, 8(1): 9883. https://doi.org/10.1038/s41598-018-28118-1

[157]

Ali W, Mishra S, Rizvi A, et al., 2021, Circulating microRNA-126 as an independent risk predictor of coronary artery disease: A case-control study. EJIFCC, 32(3): 347–362.

[158]

Lan F, Qing Q, Pan Q, et al., 2018, Serum exosomal miR- 301a as a potential diagnostic and prognostic biomarker for human glioma. Cell Oncol (Dordrecht), 41(1): 25–33. https://doi.org/10.1007/s13402-017-0355-3

[159]

Tang Y, Zhao Y, Song X, et al., 2019, Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer. J Clin Lab Anal, 33(9): e23004. https://doi.org/10.1002/jcla.23004 

[160]

Guo CM, Liu SQ, Sun MZ, 2020, miR-429 as biomarker for diagnosis, treatment and prognosis of cancers and its potential action mechanisms: A systematic literature review. Neoplasma, 67(2): 215–228. https://doi.org/10.4149/neo_2019_190401n282

[161]

Zhao T, Meng W, Chin Y, et al., 2021, Identification of miR‑25‑3p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer. Mol Med Rep, 23(6): 406. https://doi.org/10.3892/mmr.2021.12045

[162]

Zhang J, Li D, Zhang R, et al., 2020, The miR-21 potential of serving as a biomarker for liver diseases in clinical practice. Biochem Soc Trans, 48(5): 2295–2305. https://doi.org/10.1042/bst20200653

[163]

Han J, Li J, Qian Y, et al., 2109, Identification of plasma miR-148a as a noninvasive biomarker for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol, 43(5): 585–593.

[164]

Chew JR, Chuah SJ, Teo KY, et al., 2019, Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomater, 89: 252–264. https://doi.org/10.1016/j.actbio.2019.03.021

[165]

Oishi Y, Manabe I, 2018, Macrophages in inflammation, repair and regeneration. Int Immunol, 30(11): 511–528. 

[166]

Wang R, Ji Q, Meng C, et al., 2020, Role of gingival mesenchymal stem cell exosomes in macrophage polarization under inflammatory conditions. Int Immunopharmacol, 81: 106030. https://doi.org/10.1016/j.intimp.2019.106030

[167]

Liao W, Du Y, Zhang C, et al., 2019, Exosomes: The next generation of endogenous nanomaterials for advanced drug delivery and therapy. Acta Biomater, 86: 1–14. https://doi.org/10.1016/j.actbio.2018.12.045

[168]

Mohammed E, Khalil E, Sabry D, 2018, Effect of adipose-derived stem cells and their exo as adjunctive therapy to nonsurgical periodontal treatment: A histologic and histomorphometric study in rats. Biomolecules, 8(4): 167. https://doi.org/10.3390/biom8040167

[169]

Wei J, Song Y, Du Z, et al., 2020, Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis. J Mol Histol, 51(4): 455–466. https://doi.org/10.1007/s10735-020-09896-3

[170]

Xie Y, Hu JH, Wu H, et al., 2019, Bone marrow stem cells derived exosomes improve osteoporosis by promoting osteoblast proliferation and inhibiting cell apoptosis. Eur Rev Med Pharmacol Sci, 23(3): 1214–1220.

[171]

Nargesi AA, Lerman LO, Eirin A, 2017, Mesenchymal stem cell-derived extracellular vesicles for kidney repair: Current status and looming challenges. Stem Cell Res Ther, 8(1): 273. https://doi.org/10.1186/s13287-017-0727-7

[172]

Nagaishi K, Mizue Y, Chikenji T, et al., 2016, Mesenchymal stem cell therapy ameliorates diabetic nephropathy via the paracrine effect of renal trophic factors including exosomes. Sci Rep, 6: 34842. https://doi.org/10.1038/srep34842

[173]

Sato YT, Umezaki K, Sawada S, et al., 2016, Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep, 6: 21933. https://doi.org/10.1038/srep21933

[174]

Li Y, Ren C, Li H, et al., 2019, Role of exosomes induced by remote ischemic preconditioning in neuroprotection against cerebral ischemia. Neuroreport, 30(12): 834–841. https://doi.org/10.1097/wnr.0000000000001280 

[175]

Inoue T, Sugiyama M, Hattori H, et al., 2013, Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A, 19(1–2): 24–29. https://doi.org/10.1089/ten.tea.2011.0385

[176]

Chen GH, Xu J, Yang YJ, 2017, Exosomes: Promising sacks for treating ischemic heart disease? Am J Physiol Heart Circ Physiol, 313(3): H508–H523. https://doi.org/10.1152/ajpheart.00213.2017

[177]

Luo Q, Guo D, Liu G, et al., 2017, Exosomes from MiR- 126-overexpressing adscs are therapeutic in relieving acute myocardial ischaemic injury. Cell Physiol Biochem, 44(6): 2105–2116. https://doi.org/10.1159/000485949

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