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Molecular imaging assessment of periodontitis lesions in an experimental mouse model

Clinical Oral Investigations volume 23, pages 821–827 (2019)Cite this article

Abstract

Objective

We aimed to evaluate molecular imaging as a novel diagnostic tool for mice periodontitis model induced by ligature and Porphyromonas gingivalis (Pg) inoculation.

Materials and methods

Twelve female mice were assigned to the following groups: no treatment as control group (n = 4); periodontitis group induced by ligature and Pg as Pg group (n = 4); and Pg group treated with glycyrrhizinic acid (GA) as Pg + GA group (n = 4). All mice were administered a myeloperoxidase (MPO) activity-specific luminescent probe and observed using a charge-coupled device camera on day 14. Image analysis on all mice was conducted using software to determine the signal intensity of inflammation. Additionally, histological and radiographic evaluation for periodontal inflammation and bone resorption at the site of periodontitis, and quantitative enzyme-linked immunosorbent assay (ELISA) were conducted on three mice for each group. Each experiment was performed three times.

Results

Levels of serum IgG antibody against P. gingivalis were significantly higher in the Pg than in the Pg + GA group. Histological analyses indicated that the number of osteoclasts and neutrophils were significantly lower in the Pg + GA than in the Pg group. Micro-CT image analysis indicated no difference in bone resorption between the Pg and Pg + GA groups. The signal intensity of MPO activity was detected on the complete craniofacial image; moreover, strong signal intensity was localized specifically at the periodontitis site in the ex vivo palate, with group-wise differences.

Conclusions

Molecular imaging analysis based on MPO activity showed high sensitivity of detection of periodontal inflammation in mice.

Clinical relevance

Molecular imaging analysis based on MPO activity has potential as a diagnostic tool for periodontitis.

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References

  1. Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820

    Article  Google Scholar 

  2. Albandar JM (2002) Global risk factors and risk indicators for periodontal diseases. Periodontol 29:177–206

    Article  Google Scholar 

  3. Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356:911–920

    Article  Google Scholar 

  4. Joss A, Adler R, Lang NP (1994) Bleeding on probing. A parameter for monitoring periodontal conditions in clinical practice. J Clin Periodontol 21:402–408

    Article  Google Scholar 

  5. Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A (2008) Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol 35:668–673

    Article  Google Scholar 

  6. Kugahara T, Shosenji Y, Ohashi K (2008) Screening for periodontitis in pregnant women with salivary enzymes. J Obstet Gynaecol Res 34:40–46

    PubMed  Google Scholar 

  7. Kudo C, Naruishi K, Maeda H, Abiko Y, Hino T, Iwata M, Mitsuhashi C, Murakami S, Nagasawa T, Nagata T, Yoneda S, Nomura Y, Noguchi T, Numabe Y, Ogata Y, Sato T, Shimauchi H, Yamazaki K, Yoshimura A, Takashiba S (2012) Assessment of the plasma/serum IgG test to screen for periodontitis. J Dent Res 91:1190–1195

    Article  Google Scholar 

  8. Mankoff DA (2007) A definition of molecular imaging. J Nucl Med 48:18–21

    Google Scholar 

  9. Peterson TE, Manning HC (2009) Molecular imaging: 18F-FDG PET and a whole lot more. J Nucl Med Technol 37:151–161

    Article  Google Scholar 

  10. Shimojo M, Higuchi M, Suhara T, Sahara N (2015) Imaging multimodalities for dissecting Alzheimer’s disease: advanced technologies of positron emission tomography and fluorescence imaging. Front Neurosci 22:482

    Google Scholar 

  11. Shimamoto H, Tatsumi M, Kakimoto N, Hamada S, Shimosegawa E, Murakami S, Furukawa S, Hatazawa J (2008) (18)F-FDG accumulation in the oral cavity is associated with periodontal disease and apical periodontitis: an initial demonstration on PET/CT. Ann Nucl Med 22:587–593

    Article  Google Scholar 

  12. Reinking MF, Osman MM (2009) Prospective evaluation of physiologic uptake detected with true whole-body 18F-FDG PET/CT in healthy subjects. J Nucl Med Technol 37:31–37

    Article  Google Scholar 

  13. Cao CF, Smith QT (1989) Crevicular fluid myeloperoxidase at healthy. gingivitis and periodontitis sites J Clin Periodontol 16:17–20

    Article  Google Scholar 

  14. Cheung R, Shen F, Phillips JH, McGeachy MJ, Cua DJ, Heyworth PG, Pierce RH (2011) Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice. J Clin Invest 121:4446–4461

    Article  Google Scholar 

  15. Cernak I (2010) The importance of systemic response in the pathobiology of blast-induced neurotrauma. Front Neurol 10:151

    Google Scholar 

  16. Abe T, Hajishengallis G (2013) Optimization of the ligature-induced periodontitis model in mice. J Immunol Methods 394:49–54

    Article  Google Scholar 

  17. Sasaki H, Suzuki N, Alshwaimi E, Xu Y, Battaglino R, Morse L, Stashenko P (2010) 18β-glycyrrhetinic acid inhibits periodontitis via glucocorticoid-independent nuclear factor-κB inactivation in interleukin-10-deficient mice. J Periodontal Res 45:757–763

    Article  Google Scholar 

  18. Liu J, Nam HK, Wang E, Hatch NE (2013) Further analysis of the Crouzon mouse: effects of the FGFR2 (C342Y) mutation are cranial bone-dependent. Calcif Tissue Int 92:451–466

    Article  Google Scholar 

  19. Wilensky A, Polak D, Awawdi S, Halabi L, Shapira L, Houri-Haddad Y (2009) Strain-dependent activation of the mouse immune response is correlated with Porphyromonas gingivalis-induced experimental periodontitis. J Clin Periodontol 36:915–921

    Article  Google Scholar 

  20. Miyanishi K, Hoki T, Tanaka S, Kato J (2015) Prevention of hepatocellular carcinoma: focusing on antioxidant therapy. World J Hepatol 7:593–599

    Article  Google Scholar 

  21. Van Gelderen CE, Bijlsma JA, Van Dokkum W, Savelkoul TJ (2000) Glycyrrhizic acid: the assessment of a no effect level. Hum Exp Toxicol 19:434–439

    Article  Google Scholar 

  22. Horibe M, Watanabe H, Ishikawa I (1995) Effect of periodontal treatments on serum IgG antibody titers against periodontopathic bacteria. J Clin Periodontol 22:510–515

    Article  Google Scholar 

  23. Kroes BH, Beukelman CJ, van den Berg AJ, Wolbink GJ, van Dijk H, Labadie RP (1997) Inhibition of human complement by beta-glycyrrhetinic acid. Immunology 90:115–120

    Article  Google Scholar 

  24. Marcaccini AM, Meschiari CA, Zuardi LR, De Sousa TS, Taba M Jr, Teofilo JM, Jacob-Ferreira AL, Tanus-Santos JE, Novaes AB Jr, Gerlach RF (2010) Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. J Clin Periodontol 37:180–190

    Article  Google Scholar 

  25. Gross S, Gammon ST, Moss BL, Rauch D, Harding J, Heinecke JW, Ratner L, Piwnica-Worms D (2009) Bioluminescence imaging of myeloperoxidase activity in vivo. Nat Med 15:455–461

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank the staff at the Okayama Medical Innovation Center and Public Laboratory at Okayama University for their support in the molecular imaging study. The authors would also like to thank Dr. Mitsuaki Ono and the Department of Oral Rehabilitation and Regenerative Medicine at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences for their support in the micro-CT scanning.

Funding

This work was funded by a JSPS KAKENHI grant-in-aid for Young Scientists (B) Number JP24792327, the Kobayashi Magobe Memorial Medical Foundation, the Ryobi Teien Foundation, and a grant-in-aid for the COE projects by MEXT, Japan, titled “Center of excellence for molecular and gene targeting therapies with micro-doze molecular imaging modalities.”

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Affiliations

  1. Department of Pathophysiology - Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Hidetaka Ideguchi, Keisuke Yamashiro, Tadashi Yamamoto, Masayuki Shimoe, Shoichi Hongo, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hiroaki Aoyagi, Mari Kawamura & Shogo Takashiba

Authors
  1. Hidetaka Ideguchi
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  2. Keisuke Yamashiro
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  3. Tadashi Yamamoto
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  4. Masayuki Shimoe
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  5. Shoichi Hongo
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  6. Shinsuke Kochi
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  7. Chiaki Yoshihara-Hirata
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  8. Hiroaki Aoyagi
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  9. Mari Kawamura
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  10. Shogo Takashiba
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Corresponding author

Correspondence to Shogo Takashiba.

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This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All animal experimental protocols and procedures were approved by the Animal Care and Use Committee, Okayama University, Japan (#OKU-2014459).

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Ideguchi, H., Yamashiro, K., Yamamoto, T. et al. Molecular imaging assessment of periodontitis lesions in an experimental mouse model. Clin Oral Invest 23, 821–827 (2019). https://doi.org/10.1007/s00784-018-2510-2

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  • DOI: https://doi.org/10.1007/s00784-018-2510-2

Keywords

  • Glycyrrhizin
  • Inflammation
  • Molecular imaging
  • Myeloperoxidase
  • Periodontitis
  • Periodontal examination