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.
Similar content being viewed by others
References
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
Author information
Authors and Affiliations
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
Ethics declarations
Competing interests
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).
Consent to participate
The written informed consent of all the participating subjects was obtained prior to enrolling in this study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-023-05017-y