Top

Published in:

03-06-2022 | Bone Defect | Original Article

The optimization of ligature/bone defect-induced periodontitis model in rats

Authors: Jingyi Gao, Simin Cai, Zijie Wang, Dan Li, Minyi Ou, Xinlu Zhang, Zhihui Tian

Published in: Odontology | Issue 4/2022

Abstract

The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9–12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.

Available only for authorised users

Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44. https://doi.org/10.1038/nri3785.CrossRefPubMedPubMedCentral

Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol 2000. 2020;83(1):14–25. https://doi.org/10.1111/prd.12296.CrossRefPubMed

Wirth R, Pap B, Maróti G, Vályi P, Komlósi L, Barta N, et al. Toward personalized oral diagnosis: distinct microbiome clusters in periodontitis biofilms. Front Cell Infect Microbiol. 2021. https://doi.org/10.3389/fcimb.2021.747814.CrossRefPubMedPubMedCentral

Prucsi Z, Płonczyńska A, Potempa J, Sochalska M. Uncovering the Oral Dysbiotic Microbiota as Masters of Neutrophil Responses in the Pathobiology of Periodontitis. Front Microbiol. 2021. https://doi.org/10.3389/fmicb.2021.729717.CrossRefPubMedPubMedCentral

Socransky SS, Haffajee AD. Dental biofilms: difficult therapeutic targets. Periodontol. 2000;2002(28):12–55. https://doi.org/10.1034/j.1600-0757.2002.280102.x.CrossRef

Suárez LJ, Garzón H, Arboleda S, Rodríguez A. Oral dysbiosis and autoimmunity: from local periodontal responses to an imbalanced systemic immunity. A review. Front Immunol. 2020. https://doi.org/10.3389/fimmu.2020.591255.CrossRefPubMedPubMedCentral

Usui M, Onizuka S, Sato T, Kokabu S, Ariyoshi W, Nakashima K. Mechanism of alveolar bone destruction in periodontitis—periodontal bacteria and inflammation. Jpn Dent Sci Rev. 2021;57:201–8. https://doi.org/10.1016/j.jdsr.2021.09.005.CrossRefPubMedPubMedCentral

Yang B, Pang X, Li Z, Chen Z, Wang Y. Immunomodulation in the treatment of periodontitis: progress and perspectives. Front Immunol. 2021;12: 781378. https://doi.org/10.3389/fimmu.2021.781378.CrossRefPubMedPubMedCentral

Bouchard P, Carra MC, Boillot A, Mora F, Range H. Risk factors in periodontology: a conceptual framework. J Clin Periodontol. 2017;44(2):125–31. https://doi.org/10.1111/jcpe.12650.CrossRefPubMed

10.

Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86(5):611–22. https://doi.org/10.1902/jop.2015.140520.CrossRefPubMedPubMedCentral

11.

Hayashi K, Hasegawa Y, Takemoto Y, Cao C, Takeya H, Komohara Y, et al. Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer’s disease. Exp Gerontol. 2019;120:1–5. https://doi.org/10.1016/j.exger.2019.02.007.CrossRefPubMed

12.

Polak D, Wilensky A, Antonoglou GN, Shapira L, Goldstein M, Martin C. The efficacy of pocket elimination/reduction compared to access flap surgery: a systematic review and meta-analysis. J Clin Periodontol. 2020;47(Suppl 22):303–19. https://doi.org/10.1111/jcpe.13246.CrossRefPubMed

13.

Trofin EA, Monsarrat P, Kemoun P. Cell therapy of periodontium: from animal to human? Front Physiol. 2013;4:325. https://doi.org/10.3389/fphys.2013.00325.CrossRefPubMedPubMedCentral

14.

Pellegrini G, Seol YJ, Gruber R, Giannobile WV. Pre-clinical models for oral and periodontal reconstructive therapies. J Dent Res. 2009;88(12):1065–76. https://doi.org/10.1177/0022034509349748.CrossRefPubMedPubMedCentral

15.

Petersen A, Princ A, Korus G, Ellinghaus A, Leemhuis H, Herrera A, et al. A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects. Nat Commun. 2018;9(1):4430. https://doi.org/10.1038/s41467-018-06504-7.CrossRefPubMedPubMedCentral

16.

Shujaa Addin A, Akizuki T, Matsuura T, Hoshi S, Ikawa T, Maruyama K, et al. Histological healing after nonsurgical periodontal treatment with enamel matrix derivatives in canine experimental periodontitis. Odontology. 2018;106(3):289–96. https://doi.org/10.1007/s10266-018-0347-4.CrossRefPubMed

17.

Fawzy El-Sayed KM, Dorfer CE. (*) Animal models for periodontal tissue engineering: a knowledge-generating process. Tissue Eng Part C Methods. 2017;23(12):900–25. https://doi.org/10.1089/ten.TEC.2017.0130.CrossRefPubMed

18.

Finger Stadler A, Patel M, Pacholczyk R, Cutler CW, Arce RM. Long-term sustainable dendritic cell-specific depletion murine model for periodontitis research. J Immunol Methods. 2017;449:7–14. https://doi.org/10.1016/j.jim.2017.06.007.CrossRefPubMed

19.

Li CH, Amar S. Morphometric, histomorphometric, and microcomputed tomographic analysis of periodontal inflammatory lesions in a murine model. J Periodontol. 2007;78(6):1120–8. https://doi.org/10.1902/jop.2007.060320.CrossRefPubMed

20.

Xie R, Kuijpers-Jagtman AM, Maltha JC. Inflammatory responses in two commonly used rat models for experimental tooth movement: comparison with ligature-induced periodontitis. Arch Oral Biol. 2011;56(2):159–67. https://doi.org/10.1016/j.archoralbio.2010.09.007.CrossRefPubMed

21.

Batool F, Strub M, Petit C, Bugueno IM, Bornert F, Clauss F, et al. Periodontal tissues, maxillary jaw bone, and tooth regeneration approaches: from animal models analyses to clinical applications. Nanomaterials (Basel). 2018. https://doi.org/10.3390/nano8050337.CrossRefPubMedPubMedCentral

22.

Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, et al. Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells. 2008;26(4):1065–73. https://doi.org/10.1634/stemcells.2007-0734.CrossRefPubMed

23.

Koo KT, Polimeni G, Albandar JM, Wikesjo UM. Periodontal repair in dogs: analysis of histometric assessments in the supraalveolar periodontal defect model. J Periodontol. 2004;75(12):1688–93. https://doi.org/10.1902/jop.2004.75.12.1688.CrossRefPubMed

24.

Wang S, Liu Y, Fang D, Shi S. The miniature pig: a useful large animal model for dental and orofacial research. Oral Dis. 2007;13(6):530–7. https://doi.org/10.1111/j.1601-0825.2006.01337.x.CrossRefPubMed

25.

Vargas-Sanchez PK, Moro MG, Santos FAD, Anbinder AL, Kreich E, Moraes RM, et al. Agreement, correlation, and kinetics of the alveolar bone-loss measurement methodologies in a ligature-induced periodontitis animal model. J Appl Oral Sci. 2017;25(5):490–7. https://doi.org/10.1590/1678-7757-2016-0517.CrossRefPubMedPubMedCentral

26.

Kim SE, Lee ER, Lee Y, Jeong M, Park YW, Ahn JS, et al. A modified method for inducing periodontitis in dogs using a silk-wire twisted ligature. J Vet Sci. 2012;13(2):193–7. https://doi.org/10.4142/jvs.2012.13.2.193.CrossRefPubMedPubMedCentral

27.

Duan X, Gleason RC, Li F, Hosur KB, Duan X, Huang D, et al. Sex dimorphism in periodontitis in animal models. J Periodontal Res. 2016;51(2):196–202. https://doi.org/10.1111/jre.12298.CrossRefPubMed

28.

Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975;25(4):229–35.PubMed

29.

Yu T, Zhao L, Huang X, Xie M, Wang X, Ma C, et al. Postoperative weight loss masks metabolic impacts of periodontitis in obese rodents. J Periodontol. 2017;88(6):e97–108. https://doi.org/10.1902/jop.2017.160655.CrossRefPubMed

30.

Graves DT, Correa JD, Silva TA. The oral microbiota is modified by systemic diseases. J Dent Res. 2019;98(2):148–56. https://doi.org/10.1177/0022034518805739.CrossRefPubMed

31.

Messer JG, La S, Kipp DE, Castillo EJ, Yarrow JF, Jorgensen M, et al. Diet-induced generalized periodontitis in lewis rats. Comp Med. 2019;69(5):384–400. https://doi.org/10.30802/AALAS-CM-18-000113.CrossRefPubMedPubMedCentral

32.

Donos N, Park JC, Vajgel A, de Carvalho FB, Dereka X. Description of the periodontal pocket in preclinical models: limitations and considerations. Periodontol 2000. 2018;76(1):16–34. https://doi.org/10.1111/prd.12155.CrossRefPubMed

33.

de Molon RS, Park CH, Jin Q, Sugai J, Cirelli JA. Characterization of ligature-induced experimental periodontitis. Microsc Res Tech. 2018;81(12):1412–21. https://doi.org/10.1002/jemt.23101.CrossRefPubMed

34.

Li X, Wu X, Ma Y, Hao Z, Chen S, Fu T, et al. Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats. Arch Oral Biol. 2015;60(5):789–98. https://doi.org/10.1016/j.archoralbio.2015.01.015.CrossRefPubMed

35.

Takata T, Donath K. The mechanism of pocket formation. A light microscopic study on undecalcified human material. J Periodontol. 1988;59(4):215–21. https://doi.org/10.1902/jop.1988.59.4.215.CrossRefPubMed

36.

Page RCSH. Periodontitis in man and animals. A comparative review. Basel: Karger; 1982.

37.

Chiu HC, Chiang CY, Tu HP, Wikesjo UM, Susin C, Fu E. Effects of bone morphogenetic protein-6 on periodontal wound healing/regeneration in supraalveolar periodontal defects in dogs. J Clin Periodontol. 2013;40(6):624–30. https://doi.org/10.1111/jcpe.12075.CrossRefPubMed

38.

Kantarci A, Hasturk H, Van Dyke TE. Animal models for periodontal regeneration and peri-implant responses. Periodontol 2000. 2015;68(1):66–82. https://doi.org/10.1111/prd.12052.CrossRefPubMedPubMedCentral

39.

Marchesan J, Girnary MS, Jing L, Miao MZ, Zhang S, Sun L, et al. An experimental murine model to study periodontitis. Nat Protoc. 2018;13(10):2247–67. https://doi.org/10.1038/s41596-018-0035-4.CrossRefPubMedPubMedCentral

Title: The optimization of ligature/bone defect-induced periodontitis model in rats
Authors: Jingyi Gao
Simin Cai
Zijie Wang
Dan Li
Minyi Ou
Xinlu Zhang
Zhihui Tian
Publication date: 03-06-2022
Publisher: Springer Nature Singapore
Keyword: Bone Defect
Published in: Odontology / Issue 4/2022
Print ISSN: 1618-1247
Electronic ISSN: 1618-1255
DOI: https://doi.org/10.1007/s10266-022-00715-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The optimization of ligature/bone defect-induced periodontitis model in rats

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2022

How do carious root lesions develop after the end of professional preventive measures?—Preliminary findings of a randomized clinical trial

Upregulation of TRPA1 and reduction of NF-κB translocation could be part of the immunomodulatory process during primary tooth inflammation

Role of magnesium-doped calcium sulfate and β-tricalcium phosphate composite ceramics in macrophage polarization and osteo-induction

Does the use of fiber posts increase the fracture resistance of simulated immature teeth? A systematic review

Efficacy of concentrated growth factor with low-level laser for the regeneration of interdental papilla defects

Bevacizumab and sunitinib mediate osteogenic and pro-inflammatory molecular changes in primary human alveolar osteoblasts in vitro