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Effect of micro-osteoperforations on the gene expression profile of the periodontal ligament of orthodontically moved human teeth

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Abstract

Objectives

This study aimed to evaluate the effect of micro-osteoperforations (MOPs) on the gene expression profile of the periodontal ligament (PDL) of orthodontically moved teeth.

Materials and methods

Fifteen participants were randomly assigned into two groups: tooth movement only (Tr1, n = 7) and tooth movement supplemented with MOPs (Tr2, n = 8). In each subject, orthodontic tooth movement (OTM) was performed on premolar in one side, while no force was applied on contralateral premolar (Unt, n = 15). Seven days after loading, premolars were extracted for orthodontic reasons. RNA extraction from PDL and subsequent RNA-sequencing were performed. False discovery rates (Padj < 0.05) and log2 fold change (+ / − 1.5) thresholds were used to identify sets of differentially expressed genes (DEGs) among the groups. DEGs were analyzed with gene ontology enrichment, KEGG, and network analysis.

Results

Three hundred thirty-one DEGs were found between Tr1 and Unt, and 356 between Tr2 and Unt. Although, there were no significantly DEGs between Tr2 and Tr1, DEGs identified exclusively in Tr1 vs. Unt were different from those identified exclusively in Tr2 vs. Unt. In Tr1, genes were related to bone metabolism processes, such as osteoclast and osteoblast differentiation. In Tr2, genes were associated to inflammation processes, like inflammatory and immune responses, and cellular response to tumor necrosis factor.

Conclusions

MOPs do not significantly alter the PDL gene expression profile of orthodontically moved human teeth. This study provides for the first time evidence on the whole PDL gene expression profiles associated to OTM in humans. Novel biomarkers for OTM are suggested for additional research.

Clinical relevance

The identified biomarkers provide new insights into the molecular mechanisms that would occur when OTM is supplemented with MOPs. These markers are expected to be useful in the near future for the application of personalized strategies related to the OTM.

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References

  1. Krishnan V, Davidovitch Z (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop 129:469.e1–32

    Article  Google Scholar 

  2. Alikhani M, Sangsuwon C, Alansari S, Nervina JM, Teixeira CC (2018) Biphasic theory: breakthrough understanding of tooth movement. J World Fed Orthod 7:82–88

    Google Scholar 

  3. Chaushu S, Klein Y, Mandelboim O, Barenholz Y, Fleissig O (2021) Immune changes induced by orthodontic forces: a critical review. J Dent Res 220345211016285. [Epub ahead of print]

  4. Klein Y, Fleissig O, Polak D, Barenholz Y, Mandelboim O, Chaushu S (2020) Immunorthodontics: in vivo gene expression of orthodontic tooth movement. Sci Rep 10:8172

    Article  PubMed  PubMed Central  Google Scholar 

  5. Janjic M, Docheva D, Janjic OT, Wichelhaus A, Baumert U (2018) In vitro weight-loaded cell models for understanding mechanodependent molecular pathways involved in orthodontic tooth movement: a systematic review. Stem Cells Int 2018:3208285

    Article  PubMed  PubMed Central  Google Scholar 

  6. Spitz A, Christovam IO, Marañón-Vásquez GA, Masterson DF, Adesse D, Maia LC et al (2020) Global gene expression profile of periodontal ligament cells submitted to mechanical loading: A systematic review. Arch Oral Biol 118:104884

    Article  PubMed  Google Scholar 

  7. Meikle MC (2006) The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod 28:221–240

    Article  PubMed  Google Scholar 

  8. Pachêco-Pereira C, Pereira JR, Dick BD, Perez A (2015) Flores-Mir C Factors associated with patient and parent satisfaction after orthodontic treatment: a systematic review. Am J Orthod Dentofacial Orthop 148:652–659

    Article  PubMed  Google Scholar 

  9. Pinto AS, Alves LS, Zenkner JE, Zanatta FB, Maltz M (2017) Gingival enlargement in orthodontic patients: effect of treatment duration. Am J Orthod Dentofacial Orthop 152:477–482

    Article  PubMed  Google Scholar 

  10. Pinto AS, Alves LS, Maltz M, Susin C, Zenkner JE (2018) Does the duration of fixed orthodontic treatment affect caries activity among adolescents and young adults? Caries Res 52:463–467

    Article  PubMed  Google Scholar 

  11. Pandis N, Nasika M, Polychronopoulou A, Eliades T (2008) External apical root resorption in patients treated with conventional and self-ligating brackets. Am J Orthod Dentofacial Orthop 134:646–651

    Article  PubMed  Google Scholar 

  12. Aljabaa A, Almoammar K, Aldrees A, Huang G (2018) Effects of vibrational devices on orthodontic tooth movement: A systematic review. Am J Orthod Dentofacial Orthop 154:768–779

    Article  PubMed  Google Scholar 

  13. El-Angbawi A, McIntyre GT, Fleming PS, Bearn DR (2015) Non-surgical adjunctive interventions for accelerating tooth movement in patients undergoing fixed orthodontic treatment. Cochrane Database Syst Rev 2015:CD010887

    PubMed Central  Google Scholar 

  14. Alikhani M, Raptis M, Zoldan B, Sangsuwon C, Lee YB, Alyami B et al (2013) Effect of micro-osteoperforations on the rate of tooth movement. Am J Orthod Dentofacial Orthop 144:639–648

    Article  PubMed  Google Scholar 

  15. Shahabee M, Shafaee H, Abtahi M, Rangrazi A, Bardideh E (2020) Effect of micro-osteoperforation on the rate of orthodontic tooth movement-a systematic review and a meta-analysis. Eur J Orthod 42:211–221

    Article  PubMed  Google Scholar 

  16. Sivarajan S, Ringgingon LP, Fayed MM, Wey MC (2020) The effect of micro-osteoperforations on the rate of orthodontic tooth movement: a systematic review and meta-analysis. Am J Orthod Dentofacial Orthop 157:290–304

    Article  PubMed  Google Scholar 

  17. Frost HM (1983) The regional acceleratory phenomenon: a review. Henry Ford Hosp Med J 31:3–9

    PubMed  Google Scholar 

  18. Teixeira CC, Khoo E, Tran J, Chartres I, Liu Y, Thant LM et al (2010) Cytokine expression and accelerated tooth movement. J Dent Res 89:1135–1141

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sugimori T, Yamaguchi M, Shimizu M, Kikuta J, Hikida T, Hikida M et al (2018) Micro-osteoperforations accelerate orthodontic tooth movement by stimulating periodontal ligament cell cycles. Am J Orthod Dentofacial Orthop 154:788–796

    Article  PubMed  Google Scholar 

  20. Song JS, Hwang DH, Kim SO, Jeon M, Choi BJ, Jung HS et al (2013) Comparative gene expression analysis of the human periodontal ligament in deciduous and permanent teeth. PLoS One 8:e61231

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ryan SK, Gonzalez MV, Garifallou JP, Bennett FC, Williams KS, Sotuyo NP et al (2020) Neuroinflammation and EIF2 signaling persist despite antiretroviral treatment in an hiPSC Tri-culture Model of HIV infection. Stem Cell Rep 14:703–716

    Article  Google Scholar 

  22. Goyal A, Kwon HJ, Lee K, Garg R, Yun SY, Kim YH et al (2017) Ultra-fast next generation human genome sequencing data processing using DRAGEN TM Bio-IT processor for precision medicine. Open J Genet 7:9–19

    Article  Google Scholar 

  23. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S et al (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21

    Article  PubMed  Google Scholar 

  24. Lawrence M, Huber W, Pagès H, Aboyoun P, Carlson M, Gentleman R et al (2013) Software for computing and annotating genomic ranges. PLoS Comput Biol 9:e1003118

    Article  PubMed  PubMed Central  Google Scholar 

  25. Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550

    Article  PubMed  PubMed Central  Google Scholar 

  26. Krämer A, Green J, Pollard J, Tugendreich S (2014) Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics 30:523–530

    Article  PubMed  Google Scholar 

  27. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  Google Scholar 

  28. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10:57–63

    Article  PubMed  PubMed Central  Google Scholar 

  29. Dab S, Chen K, Flores-Mir C (2019) Short- and long-term potential effects of accelerated osteogenic orthodontic treatment: a systematic review and meta-analysis. Orthod Craniofac Res 22:61–68

    Article  PubMed  Google Scholar 

  30. Fu T, Liu S, Zhao H, Cao M, Zhang R (2019) Effectiveness and safety of minimally invasive orthodontic tooth movement acceleration: a systematic review and meta-analysis. J Dent Res 98:1469–1479

    Article  PubMed  Google Scholar 

  31. Huang H, Williams RC, Kyrkanides S (2014) Accelerated orthodontic tooth movement: molecular mechanisms. Am J Orthod Dentofacial Orthop 146:620–632

    Article  PubMed  Google Scholar 

  32. Inoue D, Kido S, Matsumoto T (2004) Transcriptional induction of FosB/DeltaFosB gene by mechanical stress in osteoblasts. J Biol Chem 279:49795–49803

    Article  PubMed  Google Scholar 

  33. Diercke K, Zingler S, Kohl A, Lux CJ, Erber R (2014) Gene expression profile of compressed primary human cementoblasts before and after IL-1β stimulation. Clin Oral Investig 18:1925–1939

    Article  PubMed  Google Scholar 

  34. Marzaioli V, McMorrow JP, Angerer H, Gilmore A, Crean D, Zocco D et al (2012) Histamine contributes to increased RANKL to osteoprotegerin ratio through altered nuclear receptor 4A activity in human chondrocytes. Arthritis Rheum 64:3290–3301

    Article  PubMed  Google Scholar 

  35. Morsczeck C, Schmalz G, Reichert TE, Völlner F, Saugspier M, Viale-Bouroncle S et al (2009) Gene expression profiles of dental follicle cells before and after osteogenic differentiation in vitro. Clin Oral Investig 13:383–391

    Article  PubMed  Google Scholar 

  36. Kang W, Wang T, Hu Z, Liu F, Sun Y, Ge S (2017) Metformin inhibits porphyromonas gingivalis lipopolysaccharide-influenced inflammatory response in human gingival fibroblasts via regulating activating transcription factor-3 expression. J Periodontol 88:e169–e178

    Article  PubMed  Google Scholar 

  37. Li Y, Li M, Tan L, Huang S, Zhao L, Tang T et al (2013) Analysis of time-course gene expression profiles of a periodontal ligament tissue model under compression. Arch Oral Biol 58:511–522

    Article  PubMed  Google Scholar 

  38. Van Dyke TE, Serhan CN (2003) Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res 82:82–90

    Article  PubMed  Google Scholar 

  39. Thomasova D, Anders HJ (2015) Cell cycle control in the kidney. Nephrol Dial Transplant 30:1622–1630

    Article  PubMed  Google Scholar 

  40. Kanzaki H, Chiba M, Shimizu Y, Mitani H (2002) Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 17:210–220

    Article  PubMed  Google Scholar 

  41. Wagner EF, Matsuo K (2003) Signalling in osteoclasts and the role of Fos/AP1 proteins. Ann Rheum Dis 62:ii83-85

    Article  PubMed  PubMed Central  Google Scholar 

  42. McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442

    Article  PubMed  Google Scholar 

  43. Li L, Han M, Li S, Wang L, Xu Y (2013) Cyclic tensile stress during physiological occlusal force enhances osteogenic differentiation of human periodontal ligament cells via ERK1/2-Elk1 MAPK pathway. DNA Cell Biol 32:488–497

    Article  PubMed  PubMed Central  Google Scholar 

  44. Calenic B, Yaegaki K, Ishkitiev N, Kumazawa Y, Imai T, Tanaka T (2013) p53-Pathway activity and apoptosis in hydrogen sulfide-exposed stem cells separated from human gingival epithelium. J Periodontal Res 48:322–330

    Article  PubMed  Google Scholar 

  45. Pilon J, Kuijpers-Jagtman AM, Maltha JC (1996) Magnitude of orthodontic forces and rate of bodily tooth movement. An experimental study. Am J Orthod Dentofacial Orthop 110:16–23

    Article  PubMed  Google Scholar 

  46. Mohammed AH, Tatakis DN, Dziak R (1989) Leukotrienes in orthodontic tooth movement. Am J Orthod Dentofacial Orthop 95:231–237

    Article  PubMed  Google Scholar 

  47. Dunn MD, Park CH, Kostenuik PJ, Kapila S, Giannobile WV (2007) Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement. Bone 41:446–455

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kirschneck C, Bauer M, Gubernator J, Proff P, Schroder A (2020) Comparative assessment of mouse models for experimental orthodontic tooth movement. Sci Rep 10:12154

    Article  PubMed  PubMed Central  Google Scholar 

  49. Holland R, Bain C, Utreja A (2019) Osteoblast differentiation during orthodontic tooth movement. Orthod Craniofac Res 22:177–182

    Article  PubMed  Google Scholar 

  50. Oliva M, Muñoz-Aguirre M, Kim-Hellmuth S, Wucher V, Gewirtz ADH, Cotter DJ et al (2020) The impact of sex on gene expression across human tissues. Science 369:eaba3066

    Article  PubMed  PubMed Central  Google Scholar 

  51. Lopes-Ramos CM, Chen CY, Kuijjer ML, Paulson JN, Sonawane AR, Fagny M et al (2020) Sex differences in gene expression and regulatory networks across 29 human tissues. Cell Rep 31:107795

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kassam I, Wu Y, Yang J, Visscher PM, McRae AF (2019) Tissue-specific sex differences in human gene expression. Hum Mol Genet 28:2976–2986

    Article  PubMed  PubMed Central  Google Scholar 

  53. Edwards JG (1968) A study of the periodontium during orthodontic rotation of teeth. Am J Orthod 54:441–461

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Ricardo Teles, who contributed to conception and design of this project. The authors would also like to express their profound appreciation and gratitude for all the ideas and insights he provided. We thank Propel Orthodontics for donating the micro-osteoperforations tips, Dr. Kantarci for his critical review of the manuscript, and Dr. Seong-Oh Kim for providing helpful suggestions.

Funding

This work was supported by the Brazilian government agency CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and by NIH/NIDCR Grants # R01-DE024767 (to FT) and U01-DE021127 (to RT).

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Authors and Affiliations

  1. Department of Pediatric Dentistry and Orthodontics, School of Dentistry, Federal University of Rio de Janeiro, Rua. Prof. Rodolpho Paulo Rocco, 325, Cidade Universitária da Universidade Federal Do Rio de Janeiro, Rio de Janeiro, RJ, 21941-617, Brazil

    Alice Spitz, Guido Artemio Marañón-Vásquez & Ana Maria Bolognese

  2. Laboratory of Structural Biology, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil Av. Brasil, 4365 - Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil

    Daniel Adesse

  3. Center for Applied Genomics USA, Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Michael Gonzalez, Renata Pellegrino & Hakon Hakonarson

  4. Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Levy Building 246, 240 South 40th Street, Philadelphia, PA, 19104 47, USA

    Flavia Teles

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  1. Alice Spitz
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Correspondence to Flavia Teles.

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Spitz, A., Adesse, D., Gonzalez, M. et al. Effect of micro-osteoperforations on the gene expression profile of the periodontal ligament of orthodontically moved human teeth. Clin Oral Invest 26, 1985–1996 (2022). https://doi.org/10.1007/s00784-021-04178-y

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