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Transcriptome analysis of human peri-implant soft tissue and periodontal gingiva: a paired design study

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Abstract

Objectives

Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the soft tissue in vivo by using paired samples and compare the differences between peri-implant soft tissue and periodontal gingiva at the transcriptional level.

Methods

Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further verification was done by quantitative real-time PCR.

Results

Totally 3549 differentially expressed genes (DEGs) were found between peri-implant and periodontal groups. The Venn diagram further identified 185 DEGs in every pair of samples, of which the enrichment analysis identified significant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokine-cytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9, and SFRP2 were verified to be upregulated in peri-implant soft tissue.

Conclusions

Peri-implant soft tissue showed altered expressions of several genes related to the cell-ECM interaction compared to periodontal gingiva.

Clinical relevance

Compared to periodontal gingiva, altered cell-ECM interactions in peri-implant may contribute to the susceptibility of peri-implant diseases. At the transcriptional level, periodontal gingiva is generally considered the appropriate control for peri-implantitis, except regarding the cell-ECM interactions.

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References

  1. Chappuis V, Araujo MG, Buser D (2017) Clinical relevance of dimensional bone and soft tissue alterations post-extraction in esthetic sites. Periodontol 2000(73):73–83. https://doi.org/10.1111/prd.12167

    Article  Google Scholar 

  2. Sanz M, Schwarz F, Herrera D, McClain P, Figuero E, Molina A, Monje A, Montero E, Pascual A, Ramanauskaite A, Renouard F, Sader R, Schiegnitz E, Urban I, Heitz-Mayfield L (2022) Importance of keratinized mucosa around dental implants: consensus report of group 1 of the DGI/SEPA/Osteology Workshop. Clin Oral Implants Res 33(Suppl 23):47–55. https://doi.org/10.1111/clr.13956

    Article  PubMed  Google Scholar 

  3. Nisapakultorn K, Suphanantachat S, Silkosessak O, Rattanamongkolgul S (2010) Factors affecting soft tissue level around anterior maxillary single-tooth implants. Clin Oral Implants Res 21(6):662–670. https://doi.org/10.1111/j.1600-0501.2009.01887.x

    Article  PubMed  Google Scholar 

  4. Isler SC, Uraz A, Kaymaz O, Cetiner D (2019) An evaluation of the relationship between peri-implant soft tissue biotype and the severity of peri-implantitis: a cross-sectional study. The Int J Oral Maxillofac Implants 34(1):187–196. https://doi.org/10.11607/jomi.6958

    Article  PubMed  Google Scholar 

  5. Monje A, Gonzalez-Martin O, Avila-Ortiz G (2023) Impact of peri-implant soft tissue characteristics on health and esthetics. J Esthet Restor Dent. https://doi.org/10.1111/jerd.13003

    Article  PubMed  Google Scholar 

  6. Avila-Ortiz G, Gonzalez-Martin O, Couso-Queiruga E, Wang HL (2020) The peri-implant phenotype. J Periodontol 91(3):283–288. https://doi.org/10.1002/JPER.19-0566

    Article  PubMed  Google Scholar 

  7. Abu Hussien H, Machtei EE, Khutaba A, Gabay E, ZigdonGiladi H (2022) Palatal soft tissue thickness around dental implants and natural teeth in health and disease: a cross sectional study. Clin Implant Dent Relat Res. https://doi.org/10.1111/cid.13171

    Article  PubMed  Google Scholar 

  8. Bienz SP, Pirc M, Papageorgiou SN, Jung RE, Thoma DS (2022) The influence of thin as compared to thick peri-implant soft tissues on aesthetic outcomes: a systematic review and meta-analysis. Clin Oral Implants Res 33(Suppl 23):56–71. https://doi.org/10.1111/clr.13789

    Article  PubMed  PubMed Central  Google Scholar 

  9. Galarraga-Vinueza ME, Tavelli L (2022) Soft tissue features of peri-implant diseases and related treatment. Clin Implant Dent Relat Res. https://doi.org/10.1111/cid.13156

    Article  PubMed  Google Scholar 

  10. Wang II, Barootchi S, Tavelli L, Wang HL (2021) The peri-implant phenotype and implant esthetic complications. Contemporary overview J Esthet Restor Dent 33(1):212–223. https://doi.org/10.1111/jerd.12709

    Article  PubMed  Google Scholar 

  11. Stefanini M, Marzadori M, Sangiorgi M, Rendon A, Testori T and Zucchelli G (2023) Complications and treatment errors in peri-implant soft tissue management. Periodontol 2000. https://doi.org/10.1111/prd.12470

  12. Thoma DS, Gil A, Hämmerle CHF and Jung RE (2022) Management and prevention of soft tissue complications in implant dentistry. Periodontol 2000 88(1):116–129. https://doi.org/10.1111/prd.12415

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lin GH, Curtis DA, Kapila Y, Velasquez D, Kan JYK, Tahir P, Avila-Ortiz G, Kao RT (2020) The significance of surgically modifying soft tissue phenotype around fixed dental prostheses: an American Academy of Periodontology best evidence review. J Periodontol 91(3):339–351. https://doi.org/10.1002/JPER.19-0310

    Article  PubMed  Google Scholar 

  14. Tavelli L, Barootchi S, Avila-Ortiz G, Urban IA, Giannobile WV, Wang HL (2021) Peri-implant soft tissue phenotype modification and its impact on peri-implant health: a systematic review and network meta-analysis. J Periodontol 92(1):21–44. https://doi.org/10.1002/JPER.19-0716

    Article  PubMed  Google Scholar 

  15. Lin CY, Kuo PY, Chiu MY, Chen ZZ, Wang HL (2022) Soft tissue phenotype modification impacts on peri-implant stability: a comparative cohort study. Clin Oral Investig 27(3):1089–1100. https://doi.org/10.1007/s00784-022-04697-2

    Article  PubMed  PubMed Central  Google Scholar 

  16. Duong HY, Roccuzzo A, Stahli A, Salvi GE, Lang NP and Sculean A (2022) Oral health-related quality of life of patients rehabilitated with fixed and removable implant-supported dental prostheses. Periodontol 2000 88(1):201–237. https://doi.org/10.1111/prd.12419

    Article  PubMed  PubMed Central  Google Scholar 

  17. Thoma DS, Strauss FJ, Mancini L, Gasser TJW and Jung RE (2022) Minimal invasiveness in soft tissue augmentation at dental implants: a systematic review and meta-analysis of patient-reported outcome measures. Periodontol 2000. https://doi.org/10.1111/prd.12465

  18. Ashurko I, Tarasenko S, Esayan A, Kurkov A, Mikaelyan K, Balyasin M, Galyas A, Kustova J, Taschieri S, Corbella S (2022) Connective tissue graft versus xenogeneic collagen matrix for soft tissue augmentation at implant sites: a randomized-controlled clinical trial. Clin Oral Investig 26(12):7191–7208. https://doi.org/10.1007/s00784-022-04680-x

    Article  PubMed  Google Scholar 

  19. Kim DM, Bassir SH, Nguyen TT (2020) Effect of gingival phenotype on the maintenance of periodontal health: an American Academy of Periodontology best evidence review. J Periodontol 91(3):311–338. https://doi.org/10.1002/JPER.19-0337

    Article  PubMed  Google Scholar 

  20. Moon IS, Berglundh T, Abrahamsson I, Linder E, Lindhe J (1999) The barrier between the keratinized mucosa and the dental implant An experimental study in the dog. J Clin Periodontol 26(10):658–663. https://doi.org/10.1034/j.1600-051x.1999.261005.x

    Article  PubMed  Google Scholar 

  21. Berglundh T, Lindhe J, Ericsson I, Marinello CP, Liljenberg B, Thomsen P (1991) The soft tissue barrier at implants and teeth. Clin Oral Implants Res 2(2):81–90. https://doi.org/10.1034/j.1600-0501.1991.020206.x

    Article  PubMed  Google Scholar 

  22. Berglundh T, Lindhe J, Jonsson K, Ericsson I (1994) The topography of the vascular systems in the periodontal and peri-implant tissues in the dog. J Clin Periodontol 21(3):189–193. https://doi.org/10.1111/j.1600-051x.1994.tb00302.x

    Article  PubMed  Google Scholar 

  23. Chen D, Wu X, Liu Q, Cai H, Huang B, Chen Z (2021) Memory B cell as an indicator of peri-implantitis status: a pilot study. Int J Oral Maxillofac Implants 36(1):86–93. https://doi.org/10.11607/jomi.8641

    Article  PubMed  Google Scholar 

  24. Martinez-Gonzalez JM, Martin-Ares M, Martinez-Rodriguez N, Barona-Dorado C, Sanz-Alonso J, Cortes-Breton-Brinkmann J, Ata-Ali J (2018) Comparison of peri-implant soft tissues in submerged versus transmucosal healing: a split mouth prospective immunohistochemical study. Arch Oral Biol 90:61–66. https://doi.org/10.1016/j.archoralbio.2018.03.004

    Article  PubMed  Google Scholar 

  25. Reuten R, Mayorca-Guiliani AE, Erler JT (2022) Matritecture: mapping the extracellular matrix architecture during health and disease. Matrix Biol Plus 14:100102. https://doi.org/10.1016/j.mbplus.2022.100102

    Article  PubMed  PubMed Central  Google Scholar 

  26. Guo T, Gulati K, Arora H, Han P, Fournier B, Ivanovski S (2021) Race to invade: understanding soft tissue integration at the transmucosal region of titanium dental implants. Dental Mater 37(5):816–831. https://doi.org/10.1016/j.dental.2021.02.005

    Article  Google Scholar 

  27. Romanos GE, Schroter-Kermani C, Weingart D, Strub JR (1995) Health human periodontal versus peri-implant gingival tissues: an immunohistochemical differentiation of the extracellular matrix. Int J Oral Maxillofac Implants 10(6):750–758

    PubMed  Google Scholar 

  28. Romanos GE, Strub JR, Bernimoulin JP (1993) Immunohistochemical distribution of extracellular matrix proteins as a diagnostic parameter in healthy and diseased gingiva. J Periodontol 64(2):110–119. https://doi.org/10.1902/jop.1993.64.2.110

    Article  PubMed  Google Scholar 

  29. Lindhe J, Berglundh T (1998) The interface between the mucosa and the implant. Periodontol 2000 17:47–54. https://doi.org/10.1111/j.1600-0757.1998.tb00122.x

    Article  PubMed  Google Scholar 

  30. Liu Z, Ma S, Lu X, Zhang T, Sun Y, Feng W, Zheng G, Sui L, Wu X, Zhang X, Gao P (2019) Reinforcement of epithelial sealing around titanium dental implants by chimeric peptides. Chem Engine J 356(15):117–129. https://doi.org/10.1016/j.cej.2018.09.004

    Article  Google Scholar 

  31. Yamada KM, Sixt M (2019) Mechanisms of 3D cell migration. Nat Rev Mol Cell Biol 20(12):738–752. https://doi.org/10.1038/s41580-019-0172-9

    Article  PubMed  Google Scholar 

  32. Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK (2016) Extracellular matrix structure. Adv Drug Deliv Rev 97:4–27. https://doi.org/10.1016/j.addr.2015.11.001

    Article  PubMed  Google Scholar 

  33. Chiquet M Katsaros C and Kletsas D (2015) Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair. Periodontol 2000 68(1):21–40. https://doi.org/10.1111/prd.12076

    Article  PubMed  Google Scholar 

  34. Schwarz F, Derks J, Monje A, Wang HL (2018) Peri-implantitis. J Periodontol 89(Suppl 1):S267–S290. https://doi.org/10.1002/JPER.16-0350

    Article  PubMed  Google Scholar 

  35. Liu Y, Liu Q, Li Z, Acharya A, Chen D, Chen Z, Mattheos N, Chen Z, Huang B (2020) Long non-coding RNA and mRNA expression profiles in peri-implantitis vs periodontitis. J Periodontal Res 55(3):342–353. https://doi.org/10.1111/jre.12718

    Article  PubMed  Google Scholar 

  36. Stevens JR, Herrick JS, Wolff RK, Slattery ML (2018) Power in pairs: assessing the statistical value of paired samples in tests for differential expression. BMC Genomics 19(1):953. https://doi.org/10.1186/s12864-018-5236-2

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hein MY, Hubner NC, Poser I, Cox J, Nagaraj N, Toyoda Y, Gak IA, Weisswange I, Mansfeld J, Buchholz F, Hyman AA, Mann M (2015) A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163(3):712–723. https://doi.org/10.1016/j.cell.2015.09.053

    Article  PubMed  Google Scholar 

  38. Feld L, Kellerman L, Mukherjee A, Livne A, Bouchbinder E, Wolfenson H (2020) Cellular contractile forces are nonmechanosensitive. Sci Adv 6(17):eaaz997. https://doi.org/10.1126/sciadv.aaz6997

    Article  Google Scholar 

  39. Hinz B (2010) The myofibroblast: paradigm for a mechanically active cell. J Biomech 43(1):146–155. https://doi.org/10.1016/j.jbiomech.2009.09.020

    Article  PubMed  Google Scholar 

  40. Nan L, Zheng Y, Liao N, Li S, Wang Y, Chen Z, Wei L, Zhao S, Mo S (2019) Mechanical force promotes the proliferation and extracellular matrix synthesis of human gingival fibroblasts cultured on 3D PLGA scaffolds via TGF-beta expression. Mol Med Rep 19(3):2107–2114. https://doi.org/10.3892/mmr.2019.9882

    Article  PubMed  PubMed Central  Google Scholar 

  41. Che C, Liu J, Yang J, Ma L, Bai N, Zhang Q (2018) Osteopontin is essential for IL-1beta production and apoptosis in peri-implantitis. Clin Implant Dent Relat Res 20(3):384–392. https://doi.org/10.1111/cid.12592

    Article  PubMed  Google Scholar 

  42. Pandruvada SN, Gonzalez OA, Kirakodu S, Gudhimella S, Stromberg AJ, Ebersole JL, Orraca L, Gonzalez-Martinez J, Novak MJ, Huja SS (2016) Bone biology-related gingival transcriptome in ageing and periodontitis in non-human primates. J Clin Periodontol 43(5):408–417. https://doi.org/10.1111/jcpe.12528

    Article  PubMed  PubMed Central  Google Scholar 

  43. van der Windt GJ, Wiersinga WJ, Wieland CW, Tjia IC, Day NP, Peacock SJ, Florquin S and van der Poll T (2010) Osteopontin impairs host defense during established gram-negative sepsis caused by Burkholderia pseudomallei (melioidosis). PLoS Negl Trop Dis 4(8). https://doi.org/10.1371/journal.pntd.0000806

  44. Kaur A, Webster MR, Marchbank K, Behera R, Ndoye A, Kugel CH 3rd, Dang VM, Appleton J, O’Connell MP, Cheng P, Valiga AA, Morissette R, McDonnell NB, Ferrucci L, Kossenkov AV, Meeth K, Tang HY, Yin X, Wood WH 3rd, Lehrmann E, Becker KG, Flaherty KT, Frederick DT, Wargo JA, Cooper ZA, Tetzlaff MT, Hudgens C, Aird KM, Zhang R, Xu X, Liu Q, Bartlett E, Karakousis G, Eroglu Z, Lo RS, Chan M, Menzies AM, Long GV, Johnson DB, Sosman J, Schilling B, Schadendorf D, Speicher DW, Bosenberg M, Ribas A, Weeraratna AT (2016) sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance. Nature 532(7598):250–254. https://doi.org/10.1038/nature17392

    Article  PubMed  PubMed Central  Google Scholar 

  45. Chatzopoulos GS, Koidou VP, Wolff LF (2022) Expression of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after non-surgical periodontal treatment: a systematic review. J Periodontal Res 57(4):698–710. https://doi.org/10.1111/jre.13029

    Article  PubMed  Google Scholar 

  46. Zhou M, Jiao L, Liu Y (2019) sFRP2 promotes airway inflammation and Th17/Treg imbalance in COPD via Wnt/beta-catenin pathway. Respir Physiol Neurobiol 270:103282. https://doi.org/10.1016/j.resp.2019.103282

    Article  PubMed  Google Scholar 

  47. Mahanonda R, Champaiboon C, Subbalekha K, Sa-Ard-Iam N, Yongyuth A, Isaraphithakkul B, Rerkyen P, Charatkulangkun O, Pichyangkul S (2018) Memory T cell subsets in healthy gingiva and periodontitis tissues. J Periodontol 89(9):1121–1130. https://doi.org/10.1002/JPER.17-0674

    Article  PubMed  Google Scholar 

  48. Tomasi C, Tessarolo F, Caola I, Piccoli F, Wennstrom JL, Nollo G, Berglundh T (2016) Early healing of peri-implant mucosa in man. J Clin Periodontol 43(10):816–824. https://doi.org/10.1111/jcpe.12591

    Article  PubMed  Google Scholar 

  49. Serichetaphongse P, Chengprapakorn W, Thongmeearkom S, Pimkhaokham A (2020) Immunohistochemical assessment of the peri-implant soft tissue around different abutment materials: a human study. Clin Implant Dent Relat Res 22(5):638–646. https://doi.org/10.1111/cid.12942

    Article  PubMed  Google Scholar 

  50. Sculean A, Gruber R, Bosshardt DD (2014) Soft tissue wound healing around teeth and dental implants. J Clin Periodontol 41(Suppl 15):S6-22. https://doi.org/10.1111/jcpe.12206

    Article  PubMed  Google Scholar 

  51. Bednarz-Misa I, Neubauer K, Zacharska E, Kapturkiewicz B, Krzystek-Korpacka M (2020) Whole blood ACTB, B2M and GAPDH expression reflects activity of inflammatory bowel disease, advancement of colorectal cancer, and correlates with circulating inflammatory and angiogenic factors: relevance for real-time quantitative PCR. Adv Clin Exp Med 29(5):547–556. https://doi.org/10.17219/acem/118845

    Article  PubMed  Google Scholar 

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Funding

This study was supported by funding from the National Natural Science Foundation of China (82201095, 82271005, 81970975, and 81600914); the Guangdong Basic and Applied Basic Research Foundation, China (Nos. 2021A1515010821 and 2021A1515110303); the Science and Technology Program of Guangzhou, China (No. 202102021198); the Guangdong Financial Fund for High-Caliber Hospital Construction, China (No. 174–2018-XMZC-0001–03-0125/D-10); and the Medical Science Research Foundation of Guangdong Province, China (No. A2018422).

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Contributions

Danying Chen was responsible for the transcriptomic analysis and the manuscript drafting. Zhixin Li was responsible for the qPCR analysis. Qifan Liu, Yue Sun, Zhipeng Li, Jieting Yang, and Jiaying Song were responsible for sample processing. Zhicai Feng, Huaxiong Cai, and Baoxin Huang were responsible for interpretation of results and manuscript polishing. Baoxin Huang and Zhuofan Chen conducted the clinical surgeries and supervised the studies.

Corresponding authors

Correspondence to Zhuofan Chen or Baoxin Huang.

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The authors declare no competing interests.

Ethics approval

The current study was conducted in accordance with the World Medical Association Declaration of Helsinki (version, 2013). The ethical approval was obtained from the Ethical Committee of Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University (Ethics number: ERC-2016–21).

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The written informed consent of all the participating subjects was obtained prior to enrolling in this study.

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Chen, D., Li, Z., Li, Z. et al. Transcriptome analysis of human peri-implant soft tissue and periodontal gingiva: a paired design study. Clin Oral Invest 27, 3937–3948 (2023). https://doi.org/10.1007/s00784-023-05017-y

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