Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
권호 표지
DOI QR코드

DOI QR Code

Changes in the components of salivary exosomes due to initial periodontal therapy

  • Arisa Yamaguchi (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Yuto Tsuruya (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Kazuma Igarashi (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Zhenyu Jin (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Mizuho Yamazaki-Takai (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Hideki Takai (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Yohei Nakayama (Department of Periodontology, Nihon University School of Dentistry at Matsudo) ;
  • Yorimasa Ogata (Department of Periodontology, Nihon University School of Dentistry at Matsudo)
  • Received : 2022.08.25
  • Accepted : 2022.12.12
  • Published : 2023.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Exosomes are membrane vesicles that are present in body fluids and contain proteins, lipids, and microRNA (miRNA). Periodontal tissue examinations assess the degree of periodontal tissue destruction according to the probing depth (PD), clinical attachment loss (CAL), bleeding on probing, and X-ray examinations. However, the accurate evaluation of the prognosis of periodontitis is limited. In this study, we collected saliva from patients before and after initial periodontal therapy (IPT) and compared changes in the clinical parameters of periodontitis with changes in the components of salivary exosomes. Methods: Saliva was collected from patients with stage III and IV periodontitis at the first visit and post-IPT. Exosomes were purified from the saliva, and total protein and RNA were extracted. Changes in expression levels of C6, CD81, TSG101, HSP70, and 6 kinds of miRNA were analyzed by western blots and real-time polymerase chain reaction. Results: Patients with increased C6 expression after IPT had significantly higher levels of periodontal inflamed surface area (PISA), miR-142, and miR-144 before and after IPT than patients with decreased C6 expression after IPT. Patients with decreased and unchanged CD81 expression after IPT showed significantly higher PD, CAL, and PISA before IPT than after IPT. Patients with decreased and unchanged TSG101 expression after IPT had significantly higher PD before IPT than after IPT. Patients with increased HSP70 expression after IPT had significantly higher PD and PISA before and after IPT than patients with unchanged HSP70 after IPT. The expression levels of miR-142, miR-144, miR-200b, and miR-223 changed with changes in the levels of C6, CD81, TSG101, and HSP70 in the salivary exosomes of periodontitis patients before and after IPT. Conclusions: The expression levels of proteins and miRNAs in salivary exosomes significantly changed after IPT in periodontitis patients, suggesting that the components of exosomes could serve as biomarkers for periodontitis.

Keywords

Acknowledgement

This study was supported in part by the Japan Society for the Promotion of Science KAKENHI Grands, Grant-in-Aid for Scientific Research (C), No. 18K09583 and 21K09922 to HT, 18K09582 and 21K09921 to YN, 17K11994 and 20K09945 to YO, and a Grant-in-Aid for Research Activity Start-up and Early-Career Scientists, No. 19K21385 and 21K16976 to MYT.

References

  1. Zheng X, Chen F, Zhang J, Zhang Q, Lin J. Exosome analysis: a promising biomarker system with special attention to saliva. J Membr Biol 2014;247:1129-36. https://doi.org/10.1007/s00232-014-9717-1
  2. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012;1820:940-8. https://doi.org/10.1016/j.bbagen.2012.03.017
  3. Huang X, Hu X, Zhao M, Zhang Q. Analysis of salivary exosomal proteins in young adults with severe periodontitis. Oral Dis 2020;26:173-81. https://doi.org/10.1111/odi.13217
  4. Lin K, Zhang L, Kong M, Yang M, Chen Y, Poptic E, et al. Development of an anti-human complement C6 monoclonal antibody that inhibits the assembly of membrane attack complexes. Blood Adv 2020;4:2049-57. https://doi.org/10.1182/bloodadvances.2020001690
  5. Ma H, Chen Y, Yu M, Chen X, Qi L, Wei S, et al. Immune role of the complement component 6 gene and its associated novel miRNA, miR-727, in half-smooth tongue sole (Cynoglossus semilaevis). Dev Comp Immunol 2021;123:104156.
  6. Jin Y, Takeda Y, Kondo Y, Tripathi LP, Kang S, Takeshita H, et al. Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging. Sci Rep 2018;8:5145.
  7. Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer 2014;14:49-60. https://doi.org/10.1038/nrc3640
  8. Ferraiuolo RM, Manthey KC, Stanton MJ, Triplett AA, Wagner KU. The multifaceted roles of the tumor susceptibility gene 101 (TSG101) in normal development and disease. Cancers (Basel) 2020;12:450.
  9. Fernandez-Fernandez MR, Valpuesta JM. Hsp70 chaperone: a master player in protein homeostasis. F1000 Res 2018;7:F1000.
  10. Sevin M, Girodon F, Garrido C, de Thonel A. HSP90 and HSP70: implication in inflammation processes and therapeutic approaches for myeloproliferative neoplasms. Mediators Inflamm 2015;2015:970242.
  11. Deiuliis JA. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. Int J Obes 2016;40:88-101. https://doi.org/10.1038/ijo.2015.170
  12. Essandoh K, Li Y, Huo J, Fan GC. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock 2016;46:122-31. https://doi.org/10.1097/SHK.0000000000000604
  13. Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, et al. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol 2020;47 Suppl 22:4-60. https://doi.org/10.1111/jcpe.13290
  14. Nik Mohamed Kamal NN, Awang RA, Mohamad S, Shahidan WN. Plasma- and saliva exosome profile reveals a distinct microRNA signature in chronic periodontitis. Front Physiol 2020;11:587381.
  15. Fujimori K, Yoneda T, Tomofuji T, Ekuni D, Azuma T, Maruyama T, et al. Detection of salivary miRNAs reflecting chronic periodontitis: a pilot study. Molecules 2019;24:1034.
  16. Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med 2015;7:293ra104.
  17. Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol 2008;35:668-73. https://doi.org/10.1111/j.1600-051X.2008.01249.x
  18. Tobon-Arroyave SI, Celis-Mejia N, Cordoba-Hidalgo MP, Isaza-Guzman DM. Decreased salivary concentration of CD9 and CD81 exosome-related tetraspanins may be associated with the periodontal clinical status. J Clin Periodontol 2019;46:470-80. https://doi.org/10.1111/jcpe.13099
  19. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim) 2017;11:72-80.
  20. Bui FQ, Almeida-da-Silva CL, Huynh B, Trinh A, Liu J, Woodward J, et al. Association between periodontal pathogens and systemic disease. Biomed J 2019;42:27-35. https://doi.org/10.1016/j.bj.2018.12.001
  21. Maekawa T, Abe T, Hajishengallis E, Hosur KB, DeAngelis RA, Ricklin D, et al. Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol 2014;192:6020-7.
  22. Sarma JV, Ward PA. The complement system. Cell Tissue Res 2011;343:227-35. https://doi.org/10.1007/s00441-010-1034-0
  23. Damgaard C, Holmstrup P, Van Dyke TE, Nielsen CH. The complement system and its role in the pathogenesis of periodontitis: current concepts. J Periodontal Res 2015;50:283-93. https://doi.org/10.1111/jre.12209
  24. Morgan BP, Gasque P. Extrahepatic complement biosynthesis: where, when and why? Clin Exp Immunol 1997;107:1-7.
  25. Modinger Y, Loffler B, Huber-Lang M, Ignatius A. Complement involvement in bone homeostasis and bone disorders. Semin Immunol 2018;37:53-65. https://doi.org/10.1016/j.smim.2018.01.001
  26. Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 2019;11:30.
  27. Hajishengallis G. Complement and periodontitis. Biochem Pharmacol 2010;80:1992-2001. https://doi.org/10.1016/j.bcp.2010.06.017
  28. Raisz LG, Sandberg AL, Goodson JM, Simmons HA, Mergenhagen SE. Complement-dependent stimulation of prostaglandin synthesis and bone resorption. Science 1974;185:789-91. https://doi.org/10.1126/science.185.4153.789
  29. Hasezaki T, Yoshima T, Mine Y. Anti-CD81 antibodies reduce migration of activated T lymphocytes and attenuate mouse experimental colitis. Sci Rep 2020;10:6969.
  30. Fujii Y, Arai Y, Nakagawa S, Yamasaki T, Iijima M, Yamada N, et al. CD81 inhibition with the cytoplasmic RNA vector producing anti-CD81 antibodies suppresses arthritis in a rat CIA model. Biochem Biophys Res Commun 2022;604:22-9. https://doi.org/10.1016/j.bbrc.2022.02.081
  31. Essandoh K, Wang X, Huang W, Deng S, Gardner G, Mu X, et al. Tumor susceptibility gene 101 ameliorates endotoxin-induced cardiac dysfunction by enhancing Parkin-mediated mitophagy. J Biol Chem 2019;294:18057-68.
  32. Onishi M, Yamano K, Sato M, Matsuda N, Okamoto K. Molecular mechanisms and physiological functions of mitophagy. EMBO J 2021;40:e104705.
  33. Motahari P, Pourzare Mehrbani S, Jabbarvand H. Evaluation of salivary level of heat shock protein 70 in patients with chronic periodontitis. J Dent (Shiraz) 2021;22:175-9.
  34. Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A, et al. Heat shock protein 70: role in antigen presentation and immune stimulation. Int J Hyperthermia 2002;18:563-75. https://doi.org/10.1080/02656730210166140
  35. Murase Y, Shimizu K, Tanimura Y, Hanaoka Y, Watanabe K, Kono I, et al. Salivary extracellular heat shock protein 70 (eHSP70) levels increase after 59 min of intense exercise and correlate with resting salivary secretory immunoglobulin A (SIgA) levels at rest. Cell Stress Chaperones 2016;21:261-9. https://doi.org/10.1007/s12192-015-0656-2
  36. Li S, Song Z, Dong J, Shu R. microRNA-142 is upregulated by tumor necrosis factor-alpha and triggers apoptosis in human gingival epithelial cells by repressing BACH2 expression. Am J Transl Res 2017;9:175-83.
  37. Elazazy O, Amr K, Abd El Fattah A, Abouzaid M. Evaluation of serum and gingival crevicular fluid microRNA-223, microRNA-203 and microRNA-200b expression in chronic periodontitis patients with and without diabetes type 2. Arch Oral Biol 2021;121:104949.
  38. Nisha KJ, Janam P, Harshakumar K. Identification of a novel salivary biomarker miR-143-3p for periodontal diagnosis: a proof of concept study. J Periodontol 2019;90:1149-59. https://doi.org/10.1002/JPER.18-0729
  39. Xie Z, Chen G, Zhang X, Li D, Huang J, Yang C, et al. Salivary microRNAs as promising biomarkers for detection of esophageal cancer. PLoS One 2013;8:e57502.
  40. Ogata Y, Matsui S, Kato A, Zhou L, Nakayama Y, Takai H. MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients. J Oral Sci 2014;56:253-60. https://doi.org/10.2334/josnusd.56.253