Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Recent Advances of Therapeutic Targets for the Treatment of Periodontal Disease

  • Kim, Woo Jin (Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Soh, Yunjo (Laboratory of Pharmacology, School of Pharmacy and Institute of New Drug Development, Jeonbuk National University) ;
  • Heo, Seok-Mo (Department of Periodontology, School of Dentistry, Jeonbuk National University)
  • Received : 2021.01.04
  • Accepted : 2021.01.29
  • Published : 2021.05.01
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Abstract

Periodontal disease is primarily associated with bacterial infection such as dental plaque. Dental plaque, an oral biofilm harboring a complex microbial community, can cause various inflammatory reactions in periodontal tissue. In many cases, the local bacterial invasion and host-mediated immune responses lead to severe alveolar bone destruction. To date, plaque control, non-surgical, and surgical interventions have been the conventional periodontal treatment modalities. Although adjuvant therapies including antibiotics or supplements have accompanied these procedures, their usage has been limited by antibiotic resistance, as well as their partial effectiveness. Therefore, new strategies are needed to control local inflammation in the periodontium and host immune responses. In recent years, target molecules that modulate microbial signaling mechanisms, host inflammatory substances, and bone immune responses have received considerable attention by researchers. In this review, we introduce three approaches that suggest a way forward for the development of new treatments for periodontal disease; (1) quorum quenching using quorum sensing inhibitors, (2) inflammasome targeting, and (3) use of FDA-approved anabolic agents, including Teriparatide and sclerostin antibody.

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References

  1. Albandar, J. M. and Rams, T. E. (2002) Global epidemiology of periodontal diseases: an overview. Periodontol. 2000 29, 7-10. https://doi.org/10.1034/j.1600-0757.2002.290101.x
  2. Balli, U., Aydogdu, A. , Dede, F. O., Turer, C. C. and Guven, B. (2015) Gingival crevicular fluid levels of sclerostin, osteoprotegerin, and receptor activator of nuclear factor-kappa B ligand in periodontitis. J. Periodontol. 86, 1396-1404. https://doi.org/10.1902/jop.2015.150270
  3. Baron, R. and Kneissel, M. (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat. Med. 19, 179-192. https://doi.org/10.1038/nm.3074
  4. Bashutski, J. D., Eber, R. M., Kinney, J. S., Benavides, E., Maitra, S., Braun, T. M., Giannobile, W. V. and McCauley, L. K. (2010) Teriparatide and osseous regeneration in the oral cavity. N. Engl. J. Med. 363, 2396-2405. https://doi.org/10.1056/NEJMoa1005361
  5. Bashutski, J. D., Kinney, J. S., Benavides, E., Maitra, S., Braun, T. M., Giannobile, W. V., McCauley, L. K. and Eber, R. M. (2012) Systemic teriparatide administration promotes osseous regeneration of an intrabony defect: a case report. Clin. Adv. Periodontics 2, 66-71. https://doi.org/10.1902/cap.2012.110043
  6. Biradar, B. and Devi, P. (2011) Quorum sensing in plaque biofilms: challenges and future prospects. J. Contemp. Dent. Pract. 12, 479-485. https://doi.org/10.5005/jp-journals-10024-1080
  7. Boyden, L. M., Mao, J. H., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D. Q., Insogna, K. and Lifton, R. P. (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346, 1513-1521. https://doi.org/10.1056/NEJMoa013444
  8. Caton, J. G., Armitage, G., Berglundh, T., Chapple, I. L. C., Jepsen, S., Kornman, K. S., Mealey, B. L., Papapanou, P. N., Sanz, M. and Tonetti, M. S. (2018) A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J. Periodontol. 89, S1-S8. https://doi.org/10.1002/jper.18-0157
  9. Deas, D. E., Moritz, A. J., Sagun, R. S., Jr., Gruwell, S. F. and Powell, C. A. (2016) Scaling and root planing vs. conservative surgery in the treatment of chronic periodontitis. Periodontol. 2000 71, 128-139. https://doi.org/10.1111/prd.12114
  10. Federle, M. J. and Bassler, B. L. (2003) Interspecies communication in bacteria. J. Clin. Invest. 112, 1291-1299. https://doi.org/10.1172/JCI20195
  11. Filoche, S., Wong, L. and Sissons, C. H. (2010) Oral biofilms: emerging concepts in microbial ecology. J. Dent. Res. 89, 8-18. https://doi.org/10.1177/0022034509351812
  12. Fujita, T., Meguro, T., Fukuyama, R., Nakamuta, H. and Koida, M. (2002) New signaling pathway for parathyroid hormone and cyclic AMP action on extracellular-regulated kinase and cell proliferation in bone cells. Checkpoint of modulation by cyclic AMP. J. Biol. Chem. 277, 22191-22200. https://doi.org/10.1074/jbc.M110364200
  13. Isaza-Guzman, D. M., Medina-Piedrahita, V. M., Gutierrez-Henao, C. and Tobon-Arroyave, S. I. (2017) Salivary levels of NLRP3 inflammasome-related proteins as potential biomarkers of periodontal clinical status. J. Periodontol. 88, 1329-1338. https://doi.org/10.1902/jop.2017.170244
  14. Jilka, R. L., Weinstein, R. S., Bellido, T., Roberson, P., Parfitt, A. M. and Manolagas, S. C. (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J. Clin. Invest. 104, 439-446. https://doi.org/10.1172/JCI6610
  15. Jung, R. E., Cochran, D. L., Domken, O., Seibl, R., Jones, A. A., Buser, D. and Hammerle, C. H. (2007) The effect of matrix bound parathyroid hormone on bone regeneration. Clin. Oral Implants Res. 18, 319-325. https://doi.org/10.1111/j.1600-0501.2007.01342.x
  16. Kramer, I., Keller, H., Leupin, O. and Kneissel, M. (2010) Does osteocytic SOST suppression mediate PTH bone anabolism? Trends Endocrinol. Metab. 21, 237-244. https://doi.org/10.1016/j.tem.2009.12.002
  17. Kuchler, U., Luvizuto, E. R., Tangl, S., Watzek, G. and Gruber, R. (2011) Short-term teriparatide delivery and osseointegration: a clinical feasibility study. J. Dent. Res. 90, 1001-1006. https://doi.org/10.1177/0022034511407920
  18. Laleman, I. and Teughels, W. (2020) Novel natural product-based oral topical rinses and toothpastes to prevent periodontal diseases. Periodontol. 2000 84, 102-123. https://doi.org/10.1111/prd.12339
  19. Li, X. F., Zhang, Y. Z., Kang, H. S., Liu, W. Z., Liu, P., Zhang, J. G., Harris, S. E. and Wu, D. Q. (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883-19887. https://doi.org/10.1074/jbc.M413274200
  20. Loos, B. G. and Van Dyke, T. E. (2020) The role of inflammation and genetics in periodontal disease. Periodontol. 2000 83, 26-39. https://doi.org/10.1111/prd.12297
  21. Marchesan, J. T., Girnary, M. S., Moss, K., Monaghan, E. T., Egnatz, G. J., Jiao, Y., Zhang, S., Beck, J. and Swanson, K. V. (2020) Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics. Periodontol. 2000 82, 93-114. https://doi.org/10.1111/prd.12269
  22. Marchesan, J. T., Jiao, Y., Moss, K., Divaris, K., Seaman, W., Webster-Cyriaque, J., Zhang, S., Yu, N., Song, C., Bencharit, S., Teles, R. and Offenbacher, S. (2017) Common polymorphisms in IFI16 and AIM2 genes are associated with periodontal disease. J. Periodontol. 88, 663-672. https://doi.org/10.1902/jop.2017.160553
  23. Ominsky, M. S., Vlasseros, F., Jolette, J., Smith, S. Y., Stouch, B., Doellgast, G., Gong, J. H., Gao, Y. M., Cao, J., Graham, K., Tipton, B., Cai, J., Deshpande, R., Zhou, L., Hale, M. D., Lightwood, D. J., Henry, A. J., Popplewell, A. G., Moore, A. R., Robinson, M. K., Lacey, D. L., Simonet, W. S. and Paszty, C. (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J. Bone Miner. Res. 25, 948-959. https://doi.org/10.1002/jbmr.14
  24. Padhi, D., Jang, G., Stouch, B., Fang, L. A. and Posvar, E. (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J. Bone Miner. Res. 26, 19-26. https://doi.org/10.1002/jbmr.173
  25. Ren, Y. S., Han, X. L., Ho, S. P., Harris, S. E., Cao, Z. G., Economides, A. N., Qin, C. L., Ke, H. Z., Liu, M. and Feng, J. Q. (2015) Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model. FASEB J. 29, 2702-2711. https://doi.org/10.1096/fj.14-265496
  26. Sheridan, R. A., Wang, H. L., Eber, R. and Oh, T. J. (2015) Systemic Chemotherapeutic agents as adjunctive periodontal therapy: a narrative review and suggested clinical recommendations. J. Int. Acad. Periodontol. 17, 123-134.
  27. Suen, P. K. and Qin, L. (2016) Sclerostin, an emerging therapeutic target for treating osteoporosis and osteoporotic fracture: a general review. J. Orthop. Translat. 4, 1-13. https://doi.org/10.1016/j.jot.2015.08.004
  28. Venkatramanan, M., Sankar Ganesh, P., Senthil, R., Akshay, J., Veera Ravi, A., Langeswaran, K., Vadivelu, J., Nagarajan, S., Rajendran, K. and Shankar, E. M. (2020) Inhibition of quorum sensing and biofilm formation in Chromobacterium violaceum by fruit extracts of Passiflora edulis. ACS Omega 5, 25605-25616. https://doi.org/10.1021/acsomega.0c02483
  29. Winkler, D. G., Sutherland, M. K., Geoghegan, J. C., Yu, C. P., Hayes, T., Skonier, J. E., Shpektor, D., Jonas, M., Kovacevich, B. R., Staehling-Hampton, K., Appleby, M., Brunkow, M. E. and Latham, J. A. (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 22, 6267-6276. https://doi.org/10.1093/emboj/cdg599
  30. Xue, F., Shu, R. and Xie, Y. (2015) The expression of NLRP3, NLRP1 and AIM2 in the gingival tissue of periodontitis patients: RT-PCR study and immunohistochemistry. Arch. Oral Biol. 60, 948-958. https://doi.org/10.1016/j.archoralbio.2015.03.005
  31. Yada, S., Kamalesh, B., Sonwane, S., Guptha, I. and Swetha, R. K. (2015) Quorum sensing inhibition, relevance to periodontics. J. Int. Oral Health 7, 67-69.
  32. Yao, Y., Kauffmann, F., Maekawa, S., Sarment, L. V., Sugai, J. V., Schmiedeler, C. A., Doherty, E. J., Holdsworth, G., Kostenuik, P. J. and Giannobile, W. V. (2020) Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects. Sci. Rep. 10, 16217. https://doi.org/10.1038/s41598-020-73026-y

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