A Reappraisal of Various Animal Models used in Periodontology with Future Perspectives and Alternatives
Abstract:
Periodontitis is an inflammatory infectious disease
that occurs when the supporting tissues of the teeth are infected by a mix of gram-positive
bacteria (GPB), and anaerobic bacteria. Periodontitis must be treated as soon as
possible to avoid more injury and worsening of the condition.
Prior to evaluating new treatments, animal studies are used in conjunction with
in vitro studies in periodontitis research. Even though
cultured cells can be used to examine physiological processes that occur in periodontitis
development, the complex host response that is at the root of the illness is impossible
to replicate in vitro. Mice, rats, rabbits, hamsters, nonhuman primates, dogs, and
pigs have all been used to imitate human periodontitis, each with its own set of
benefits and drawbacks. Animals have played an important part in researching periodontal
diseases and developing effective treatments. There is a limitation in the usage
of large animals due to their housing problems. Animals for periodontitis are selected
based on their resemblance with that human structure and functioning. The usage
of these animals will aid in the better and more precise replication of human disease.
This will improve the disease’s prognosis and treatment outcome. As a result, the
medications utilized can provide a better indication of the effect they will have
on the human body based on the effects they have on animal models. Therefore, it
is critical to use appropriate animals in periodontal research in order to develop
improved treatments for these disorders. Thus, animal models play a crucial role
in periodontal research.
References:
[1] Oz, H.S., Puleo, D.A., 2011, Animal models for periodontal
disease. J Biomed Biotechnol., 2011:754857.
[2] Nazir, M., Al-Ansari, A., Al-Khalifa, K., Alhareky,
M., Gaffar, B., Almas, K., 2020, Global Prevalence of Periodontal Disease and Lack
of Its Surveillance. Scientific World Journal, 2146160.
[3] Relvas, M., López-Jarana, P., Monteiro, L., Pacheco,
J.J., Braga, A.C., Salazar, F., 2022, Study of Prevalence, Severity and Risk Factors
of Periodontal Disease in a Portuguese Population. J Clin Med., 11(13),3728.
[4] Reynolds, I., Duane, B., 2018, Periodontal disease
has an impact on patients’ quality of life. Evidence-based dentistry, 19(1),14-5.
[5] Tonetti, M.S., Bottenberg, P., Conrads, G., Eickholz,
P., Heasman, P., Huysmans, M.C., López, R., Madianos, P., Müller, F., Needleman,
I., Nyvad B., 2017, Dental caries and periodontal diseases in the ageing
population: call to action to protect and enhance oral health and well‐being as
an essential component of healthy ageing–Consensus report of group 4 of the joint
EFP/ORCA workshop on the boundaries between caries and periodontal diseases. Journal
of clinical periodontology, 44, S135-44.
[6] Pasupuleti, M.K., Molahally, S.S., Salwaji S., 2016,
Ethical guidelines, animal profile, various animal models used in periodontal
research with alternatives and future perspectives. Journal of Indian Society
of Periodontology, 20(4),360.
[7] How, K.Y., Song, K.P., Chan K.G., 2016, Porphyromonasgingivalis:
an overview of periodontopathic pathogen below the gum line. Frontiers in microbiology,
9(7), 53.
[8] Cekici, A., Kantarci, A., Hasturk, H., Van Dyke,
T.E., 2014, Inflammatory and immune pathways in the pathogenesis of periodontal
disease. Periodontology 2000, 64(1), 57-80.
[9] Zhou, L.N., Bi, C.S., Gao, L.N., An, Y., Chen, F.,
Chen, F.M., 2019, Macrophage polarization in human gingival tissue in response to
periodontal disease. Oral diseases, 25(1), 265-73.
[10] Ausenda, F., Rasperini, G., Acunzo, R., Gorbunkova,
A., Pagni, G.,2019, New perspectives in the use of biomaterials for periodontal
regeneration. Materials, 12(13), 2197.
[11] Xu, X.Y., Li, X., Wang, J., He, X.T., Sun, H.H.,
Chen, F.M.,2019, Concise review: periodontal tissue regeneration using stem cells:
strategies and translational considerations. Stem cells translational medicine,
8(4), 392-403.
[12] Struillou, X., Boutigny, H., Soueidan, A., Layrolle,
P.,2010, Experimental animal models in periodontology: a review. The open dentistry
journal, 4, 37.
[13] Martínez-García, M., Hernández-Lemus, E., 2021,
Periodontal inflammation and systemic diseases: an overview. Frontiers
in physiology, 1842.
[14] Gonzalez, OA., Nagarajan, R., Novak, M.J, Orraca,
L., Gonzalez‐Martinez, JA., Kirakodu, S.S., Ebersole, J.L., 2016, Immune system
transcriptome in gingival tissues of young nonhuman primates. Journal of periodontal
research, 51(2), 152-63.
[15] Dannan, A., Alkattan, F., 2007, Animal models in
periodontal research: A mini review of the literature. The Internet Journal of
Veterinary Medicine, 5(1), 5.
[16] Liang, Y., Luan, X., Liu, X., 2020, Recent advances
in periodontal regeneration: A biomaterial perspective, Bioactive materials,
5(2), 297-308.
[17] Sulijaya, B., Rahdewati, H., Sunarto, H., Soeroso,
Y., 2019, An. Maximizing Periodontal Defect Creation and Experimental Design in
Non-Human Primate Model Study. An Updated Review Article Journal of International
Dental and Medical Research, 12(2), 733-7.
[18] Kantarci, A., Hasturk, H., Van, Dyke., T.E., 2015,
Animal models for periodontal regeneration and peri‐implant responses. Periodontology
2000, 68(1), 66-82.
[19] Shanbhag, S., Pandis, N., Mustafa, K., Nyengaard,
J.R., Stavropoulos, A., 2017, Alveolar bone tissue engineering in critical‐size
defects of experimental animal models: a systematic review and meta‐analysis. Journal
of tissue engineering and regenerative medicine,11(10), 2935-49.
[20] Li, D., Feng, Y., Tang, H., Huang, L., Tong, Z.,
Hu, C., Chen, X., Tan, J.,2020, A simplified and effective method for generation
of experimental murine periodontitis model. Frontiers in Bioengineering and Biotechnology,
25(8),444.
[21] Marchesan, J., Girnary, MS., Jing, L., Miao, M.Z.,
Zhang, S., Sun, L., Morelli, T., Schoenfisch, M.H., Inohara, N., Offenbacher, S.,
Jiao, Y.,2018, An experimental murine model to study periodontitis. Nature protocols,13(10),
2247-67.
[22] Bhattarai, G., Poudel, SB., Kook, S.H, Lee, J.C.,2016,
Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.
Acta biomaterialia,1(29),398-408.
[23] Courbon, G., Rinaudo-Gaujous, M., Blasco-Baque,
V., Auger, I., Caire, R., Mijola, L., Vico, L., Paul, S., Marotte, H., 2019, Porphyromonasgingivalis
experimentally induces periodontitis and an anti-CCP2-associated arthritis in the
rat. Annals of the rheumatic diseases, 78(5), 594-9.
[24] Offenbacher, S., Jiao, Y., Kim, SJ., Marchesan,
J., Moss, K.L., Jing, L., Divaris, K., Bencharit, S., Agler, C.S., Morelli, T.,
Zhang, S.,2018, GWAS for Interleukin-1β levels in gingival crevicular fluid identifies
IL37 variants in periodontal inflammation. Nature communications, 9(1), 1-7.
[25] Fawzy, El-Sayed., K.M, Doerfer., C.E., 2017, Animal
models for periodontal tissue engineering: a knowledge-generating process. Tissue
Engineering Part C: Methods, 23(12), 900-25.
[26] Donos, N., Park, J.C., Vajgel, A., de, Carvalho,
Farias, B., Dereka, X., 2018, Description of the periodontal pocket in preclinical
models: limitations and considerations. Periodontology 2000, 76(1), 16-34.
[27] Jati, A.S., Furquim, L.Z., Consolaro, A., 2016,
Gingival recession: its causes and types, and the importance of orthodontic treatment.
Dental press journal of orthodontics, 21,18-29.
[28] Preshaw, P.M., 2015, Detection and diagnosis
of periodontal conditions amenable to prevention. BMC oral health, 15(1),1-1.
[29] Dahlén, G., Charalampakis, G., Abrahamsson, I.,
Bengtsson, L., Falsen, E., 2012, Predominant bacterial species in subgingival plaque
in dogs. Journal of periodontal research, 47(3), 354-64.
[30] Nicholls, V.M., Townsend, N., 2016, Dental disease
in aged horses and its management. Veterinary Clinics: Equine Practice, 32(2),
215-27.
[31] Tyrrell, K.L., Citron, D.M., Jenkins, J.R., Goldstein,
E.J., 2002, Periodontal bacteria in rabbit mandibular and maxillary abscesses. J
Clin Microbiol., 40(3):1044-7.
[32] Banu, S.R., J., 2018, A Review Role of Animal Models
in Periodontal Research. Asian Journal of Pharmaceutical and Clinical Research,
11(7),47-51.
[33] Schou, S., Holmstrup, P., Kornman, KS., 1993, A
review of the literature non-human primates used in studies of periodontal
disease pathogenesis. J Periodontol, 64,497-508.
[34] Priyanka, M., Jaiganesh, D.R.,2013, Periodontally
accelerated osteogenic orthodontics. Int J Pharm PharSci, 5,49-51.
[35] Giannobile, W.V., Finkelman, R.D., Lynch, S.E.,
1994, Comparison of canine and non-human primate animal models for periodontal regenerative
therapy: results following a single administration of PDGF/IGF-I. J Periodontol, 65(12),1158–68.
[36] Sculean, A., Karring, T., Theilade, J., Lioubavina,
N., 1997, The regenerative
potential of oxytalanfibers. an experimental study in the monkey.
J Clin Periodontol, 24(12),932–6.
[37] Kostopoulos, L., Karring, T., 2004, Susceptibility
of GTR-regenerated periodontal attachment to ligature-induced periodontitis. J Clin Periodontol,
31(5), 336–40.
[38] Karatzas, S., Zavras, A., Greenspan, D., Amar, S.,
1999, Histologic observations of periodontal wound healing after treatment with
perioglas in nonhuman primates. Int J Periodontics Rest Dent, 19(5),489–99.
[39] Donos, N., Sculean, A., Glavind, L., Reich, E.,
Karring, T., 2003, Wound healing of degree III furcation involvements following
guided tissue regeneration and/or Emdogaina histologic study. J Clin Periodontol, 30(12),1061–8.
[40] Trejo, P.M., Bonaventura, G., Weng, D., Caffesse,
RG., Bragger, U., Lang, N.P., 2006, Effect of mechanical and antiseptic therapy on peri-implant
mucositis: an experimental study in monkey. Clin Oral Implants
Res, 17(3),294–304.
[41] Sculean, A., Donos, N., Brecx, M., Reich, E., Karring,
T.,2000, Treatment of intrabony
defects with guided tissue regeneration and enamel-matrix-proteins an experimental
study in monkeys. J Clin Periodontol,
27(7), 466–72.
[42] Pieri, FA., Souza, M.C., Vermelho, L.L., Vermelho,
ML., Perciano, P.G., Vargas, F.S., Borges, A.P., da Veiga-Junior, V.F., Moreira,
M.A., 2011, Use of β-caryophyllene to combat bacterial dental plaque formation in
dogs. BMC Veterinary Research, 12(1),1-8.
[43] Yimam, M., Brownell, L., Do, S.G., Lee, Y.C., Kim,
D.S., Seo, K., Jeong, M., Kim, S., Jia, Q., 2019, Protective effect of UP446 on
ligature-induced periodontitis in beagle dogs. Dentistry Journal, 7(2),33.
[44] Hamp, S.E., Hamp, M., Olsson, S.E., Lindberg, R.,
Schauman, P.,1997, Radiography of
spontaneous periodontitis in dogs. J Periodontal Res, 32(7), 589–97.
[45] Haney, J.M., Zimmerman, G.J., Wikesjo, U.M., 1995, Periodontal repair in dogs: evaluation
of the natural disease model. J Clin Periodontol, 22(3), 208–13.
[46] Miranda, L.A., Gomes, S.C., Soares, I.J., Oppermann,
R.V., 2006, A resin-modified glass ionomer cement barrier for treating degree II
furcation defects: a pilot study in dogs. Acta Odontol Scand, 64(1),37–41.
[47] Schwarz, F., Herten, M., Sager, M., Bieling, K.,
Sculean, A., Becker, J., 2007, Comparison of naturally occurring and ligature-induced peri-implantitis bone
defects in humans and dogs. Clin Oral Implants Res 18(2),161–70.
[48] Lin, P., Niimi, H., Ohsugi, Y., Tsuchiya, Y., Shimohira,
T., Komatsu, K., Liu, A., Shiba, T., Aoki, A., Iwata, T., Katagiri, S., 2021, Application
of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of
Periodontal Disease. International Journal of Molecular Sciences, 22(16),
8900.
[49] Jacob, S.P, Nath, S., 2013, Rat gingival model for
testing drugs influencing inflammation. IeJSME, 7(2),8-16.
[50] Huang, K.K., Shen, C., Chiang, C.Y., Hsieh, Y.D.,
Fu, E., 2005, Effects of bone morphogenetic protein-6 on periodontal wound healing
in a fenestration defect of rats. J Periodontal Res, 40(1),1–10.
[51] Eslami, B., Behnia, H., Javadi, H., Khiabani, K.S.,
Saffar, A.S., 2003, Histopathologic comparison of normal and hyperplastic condyles. Oral Surg Oral Med Oral Pathol Oral RadiolEndod, 96(6),711–7.
[52] Graves, D.T., Fine, D., Teng, Y.T., Van, Dyke.,
T.E., Hajishengallis, G., 2008, The use of rodent models to investigate host–bacteria
interactions related to periodontal diseases. Journal of clinical periodontology,
35(2), 89-105.
[53] Lallam-Laroye, C., Escartin, Q., Zlowodzki, A.S.,
et al., 2006, A. Periodontitis destructions are restored by synthetic glycosaminoglycan
mimetic. J Biomed Mater Res, 79(3), 675–83.
[54] Baron, R., Saffar, J.L., 1978, A quantitative study
of bone remodeling during experimental periodontal disease in the golden hamster.
J Periodontal Res, 13(4), 309–15.
[55] Thumbigere, Math., V, Rebouças., P, Giovani., P.A.,
Puppin-Rontani, R.M., Casarin, R., Martins, L., Wang, L., Krzewski, K., Introne,
W.J., Somerman, M.J., Nociti, Jr., FH., 2018, Periodontitis in Chédiak-Higashi syndrome:
An altered immunoinflammatory response. JDR clinical & translational
research, 3(1), 35-46.
[56] Hammer, A.S., Andersen, T.H., Eriksen, T., Kortegaard,
H.E., Dietz, H.H., Chriél, M., 2005, Radiographic evaluation of destructive periodontal
disease in blue mink in relation to age and blood morphology. Canadian journal
of veterinary research, 69(2),128.
[57] Johnson-Delaney, C.A., 2016, Exotic Animal Practice.
Anatomy and disorders of the oral cavity of ferrets and other exotic companion carnivores.
Veterinary Clinics,19(3),901-28.
[58] Harper, D.S, Mann, P.H., Regnier S., 1990, Measurement
of dietary and dentifrice effects upon calculus accumulation rates in the domestic
ferret. J Dent Res, 69,447-50.
[59] Weinberg, M.A., Bral, M., 1999, Periodontol Laboratory
animal models in periodontology. J Clin, 26(6), 335–40.
[60]
Tyrrell,
K.L., Citron, D.M., Jenkins, J.R, Goldstein, E.J., Periodontal bacteria in rabbit
mandibular and maxillary abscesses. J Clin Microbiol, 40, 1044-7.
[61]
Oortgiesen,
D.A., Meijer, G.J., Bronckers, A.L., Walboomers, X.F., Jansen, J.A., 2010, Fenestration
defects in the rabbit jaw: An inadequate model for studying periodontal regeneration.
Tissue Eng Part C Methods, 16, 133-40.
[62]
Priyanka,
M., Ramamurthy, J., 2015, Tissue engineering in periodontal regeneration. Res
J Pharm Bio Chem Sci, 69,78-82.
[63]
Ranganatha,
N., Kuppast, I.J., 2012, A review on alternatives to animal testing methods in drug
development. Int J Pharm Pharm Bio Sci, 4,28-32.
[64] Holmes, M., Thomas, R., Hamerow, H., 2021, Periodontal
disease in sheep and cattle: Understanding dental health in past animal populations.
International Journal of Paleopathology, 1(33),43-54.
[65] Wang, S., Liu, Y., Fang, D., Shi, S., 2007, The
miniature pig: A useful large animal model for dental and orofacial research. Oral
Dis, 13,530-7.
[66] Polejaeva, I.A., Chen, S.H., Vaught, T.D, Page,
R.L, Mullins, J, Ball, S., et al., 2000, Cloned pigs produced by nuclear transfer
from adult somatic cells. Nature, 407,86-90.
[67] Fawzy, El-Sayed, K.M., Dörfer, C.E., 2017, Animal
Models for Periodontal Tissue Engineering: A Knowledge-Generating Process. Tissue
Eng Part C Methods, 23(12), 900-925.