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Impact of Diabetes on Periodontal Disease

  • Chapter
Diabetic Bone Disease

Abstract

Diabetes mellitus is characterized by high blood glucose levels and elevated levels of cytokines such as tumor necrosis factor (TNF), increased generation of reactive oxygen species (ROS) and the formation of advanced glycation end products that contribute to diabetic complications. Periodontitis is triggered by invasion of gingival connective tissue by bacteria or their products, which initiate a host response that leads to inflammation and loss of supporting structure of the tooth. The inflammation also interferes with the repair process so that uncoupling occurs and osteolysis is not reversed by the formation of new bone. Individuals with diabetes mellitus have greater risk of developing periodontitis as well as increased severity. Animal models have provided insight into the mechanisms by which diabetes increases periodontal bone loss by affecting critical cell types including inflammatory cells, osteoclasts, and osteoblasts. The loss of bone that is increased by hyperglycemia can be reversed by inhibition of cytokines and advanced glycation end products.

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References

  1. Bell GI, Polonsky KS. Diabetes mellitus and genetically programmed defects in beta-cell function. Nature. 2001;414(6865):788–91.

    Article  CAS  PubMed  Google Scholar 

  2. Kahn SE. Clinical review 135: the importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001;86(9):4047–58.

    CAS  PubMed  Google Scholar 

  3. Cavaghan MK, Ehrmann DA, Polonsky KS. Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J Clin Invest. 2000;106(3):329–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Preshaw PM, Bissett SM. Periodontitis: oral complication of diabetes. Endocrinol Metab Clin North Am. 2013;42(4):849–67.

    Article  PubMed  Google Scholar 

  5. Cruz NG, Sousa LP, Sousa MO, Pietrani NT, Fernandes AP, Gomes KB. The linkage between inflammation and type 2 diabetes mellitus. Diabetes Res Clin Pract. 2013;99(2):85–92.

    Article  CAS  PubMed  Google Scholar 

  6. Johnson DR, O’Connor JC, Satpathy A, Freund GG. Cytokines in type 2 diabetes. Vitam Horm. 2006;74:405–41.

    Article  CAS  PubMed  Google Scholar 

  7. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.

    Article  CAS  PubMed  Google Scholar 

  8. Nikolajczyk BS, Jagannathan-Bogdan M, Shin H, Gyurko R. State of the union between metabolism and the immune system in type 2 diabetes. Genes Immun. 2011;12(4):239–50.

    Article  CAS  PubMed  Google Scholar 

  9. Graves DT, Kayal RA. Diabetic complications and dysregulated innate immunity. Front Biosci. 2008;13:1227–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–70.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, et al. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud. 2010;7(1):15–25.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Niedowicz DM, Daleke DL. The role of oxidative stress in diabetic complications. Cell Biochem Biophys. 2005;43(2):289–330.

    Article  CAS  PubMed  Google Scholar 

  13. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002;23(5):599–622.

    Article  CAS  PubMed  Google Scholar 

  14. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414(6865):813–20.

    Article  CAS  PubMed  Google Scholar 

  15. Valkusz Z. Diabetes and osteoporosis. Orv Hetil. 2011;152(29):1161–6.

    Article  PubMed  Google Scholar 

  16. Holmberg AH, Johnell O, Nilsson PM, Nilsson J, Berglund G, Akesson K. Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int. 2006;17(7):1065–77.

    Article  CAS  PubMed  Google Scholar 

  17. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int. 2007;18(4):427–44.

    Article  CAS  PubMed  Google Scholar 

  18. Okazaki R. Management of osteoporosis in diabetes mellitus. Nihon Rinsho. 2009;67(5):1003–10.

    PubMed  Google Scholar 

  19. Lamster IB, Lalla E, Borgnakke WS, Taylor GW. The relationship between oral health and diabetes mellitus. J Am Dent Assoc. 2008;139(Suppl):19S–24.

    Article  PubMed  Google Scholar 

  20. Graves DT, Li J, Cochran DL. Inflammation and uncoupling as mechanisms of periodontal bone loss. J Dent Res. 2011;90(2):143–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Borrell LN, Papapanou PN. Analytical epidemiology of periodontitis. J Clin Periodontol. 2005;32 Suppl 6:132–58.

    Article  PubMed  Google Scholar 

  22. Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91(10):914–20.

    Article  CAS  PubMed  Google Scholar 

  23. Dye BA. Global periodontal disease epidemiology. Periodontol 2000. 2012;58(1):10–25.

    Article  PubMed  Google Scholar 

  24. Bascones-Martinez A, Gonzalez-Febles J, Sanz-Esporrin J. Diabetes and periodontal disease. Review of the literature. Am J Dent. 2014;27(2):63–7.

    PubMed  Google Scholar 

  25. Tanaka K, Miyake Y, Hanioka T, Arakawa M. Relationship between IL1 gene polymorphisms and periodontal disease in Japanese women. DNA Cell Biol. 2014;33(4):227–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Tsaousoglou P, Nietzsche S, Cachovan G, Sculean A, Eick S. Antibacterial activity of moxifloxacin on bacteria associated with periodontitis within a biofilm. J Med Microbiol. 2014;63(Pt 2):284–92.

    Article  PubMed  CAS  Google Scholar 

  27. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–20.

    Article  PubMed  Google Scholar 

  28. Junemann S, Prior K, Szczepanowski R, Harks I, Ehmke B, Goesmann A, et al. Bacterial community shift in treated periodontitis patients revealed by ion torrent 16S rRNA gene amplicon sequencing. PLoS One. 2012;7(8):e41606.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Socransky S, Haffajee A, Cugini M, Smith C, Kent RJ. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25:134–44.

    Article  CAS  PubMed  Google Scholar 

  30. Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, et al. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J. 2012;6(6):1176–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Graves DT, Oates T, Garlet GP. Review of osteoimmunology and the host response in endodontic and periodontal lesions. J Oral Microbiol. 2011;3.

    Google Scholar 

  32. Bostrom L, Bergstrom J, Dahlen G, Linder LE. Smoking and subgingival microflora in periodontal disease. J Clin Periodontol. 2001;28(3):212–9.

    Article  CAS  PubMed  Google Scholar 

  33. Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497–506.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010;89(12):1349–63.

    Article  CAS  PubMed  Google Scholar 

  35. Assuma R, Oates T, Cochran D, Amar S, Graves D. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol. 1998;160:403–9.

    CAS  PubMed  Google Scholar 

  36. Baker P, Dixon M, Evans R, Dufour L, Johnson E, Roopenian D. CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun. 1999;67:2804–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Delima A, Spyros K, Amar S, Graves DT. Inflammation and tissue loss caused by periodontal pathogens is reduced by IL-1 antagonists. J Infect Dis. 2002;186:511–6.

    Article  CAS  PubMed  Google Scholar 

  38. Teng Y, Nguyen H, Gao X, Kong Y, Gorczynski R, Singh B, et al. Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest. 2000;106:R59–67.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Han X, Kawai T, Eastcott JW, Taubman MA. Bacterial-responsive B lymphocytes induce periodontal bone resorption. J Immunol. 2006;176(1):625–31.

    Article  CAS  PubMed  Google Scholar 

  40. Williams RC, Jeffcoat MK, Kaplan ML, Goldhaber P, Johnson HG, Wechter WJ. Flurbiprofen: a potent inhibitor of alveolar bone resorption in beagles. Science. 1985;227(4687):640–2.

    Article  CAS  PubMed  Google Scholar 

  41. Hajishengallis G. Aging and its impact on innate immunity and inflammation: implications for periodontitis. J Oral Biosci. 2014;56(1):30–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Loos BG, Papantonopoulos G. Molecular biotypes for periodontal diseases? J Dent Res. 2013;92(12):1056–7.

    Article  CAS  PubMed  Google Scholar 

  43. Albert DA, Ward A, Allweiss P, Graves DT, Knowler WC, Kunzel C, et al. Diabetes and oral disease: implications for health professionals. Ann N Y Acad Sci. 2012;1255:1–15.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction? Periodontol 2000. 2014;64(1):139–53.

    Article  PubMed  Google Scholar 

  45. Tsai C, Hayes C, Taylor GW. Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent Oral Epidemiol. 2002;30(3):182–92.

    Article  PubMed  Google Scholar 

  46. Loe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16(1):329–34.

    Article  CAS  PubMed  Google Scholar 

  47. Apoorva SM, Sridhar N, Suchetha A. Prevalence and severity of periodontal disease in type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus) patients in Bangalore city: an epidemiological study. J Indian Soc Periodontol. 2013;17(1):25–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Poplawska-Kita A, Siewko K, Szpak P, Krol B, Telejko B, Klimiuk PA, et al. Association between type 1 diabetes and periodontal health. Adv Med Sci. 2014;59(1):126–31.

    Article  PubMed  Google Scholar 

  49. Leite RS, Marlow NM, Fernandes JK. Oral health and type 2 diabetes. Am J Med Sci. 2013;345(4):271–3.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Fernandes JK, Wiegand RE, Salinas CF, Grossi SG, Sanders JJ, Lopes-Virella MF, et al. Periodontal disease status in Gullah African Americans with type 2 diabetes living in South Carolina. J Periodontol. 2009;80(7):1062–8.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Al-Khabbaz AK. Type 2 diabetes mellitus and periodontal disease severity. Oral Health Prev Dent. 2014;12(1):77–82.

    PubMed  Google Scholar 

  52. Ryan ME, Carnu O, Kamer A. The influence of diabetes on the periodontal tissues. J Am Dent Assoc. 2003;134 Spec No:34S–40.

    Google Scholar 

  53. Albandar JM, Tinoco EM. Global epidemiology of periodontal diseases in children and young persons. Periodontol 2000. 2002;29:153–76.

    Article  PubMed  Google Scholar 

  54. Katagiri S, Nagasawa T, Kobayashi H, Takamatsu H, Bharti P, Izumiyama H, et al. Improvement of glycemic control after periodontal treatment by resolving gingival inflammation in type 2 diabetic patients with periodontal disease. J Diabetes Investig. 2012;3(4):402–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Naguib G, Al-Mashat H, Desta T, Graves D. Diabetes prolongs the inflammatory response to a bacterial stimulus through cytokine dysregulation. J Invest Dermatol. 2004;123:87–92.

    Article  CAS  PubMed  Google Scholar 

  56. Spite M, Serhan CN. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circ Res. 2010;107(10):1170–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Van Dyke TE. The management of inflammation in periodontal disease. J Periodontol. 2008;79(8 Suppl):1601–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. Andriankaja OM, Galicia J, Dong G, Xiao W, Alawi F, Graves DT. Gene expression dynamics during diabetic periodontitis. J Dent Res. 2012;91(12):1160–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Pacios S, Kang J, Galicia J, Gluck K, Patel H, Ovaydi-Mandel A, et al. Diabetes aggravates periodontitis by limiting repair through enhanced inflammation. FASEB J. 2012;26(4):1423–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Kang J, de Brito Bezerra B, Pacios S, Andriankaja O, Li Y, Tsiagbe V, et al. Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis. Infect Immun. 2012;80(6):2247–56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Liu R, Bal HS, Desta T, Krothapalli N, Alyassi M, Luan Q, et al. Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation. J Dent Res. 2006;85(6):510–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Li S, Dong G, Moschidis A, Ortiz J, Benakanakere MR, Kinane DF, et al. P. gingivalis modulates keratinocytes through FOXO transcription factors. PLoS One. 2013;8(11):e78541.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Pacios S, Andriankaja O, Kang J, Alnammary M, Bae J, de Brito Bezerra B, et al. Bacterial infection increases periodontal bone loss in diabetic rats through enhanced apoptosis. Am J Pathol. 2013;183(6):1928–35.

    Article  CAS  PubMed  Google Scholar 

  64. Lalla E, Cheng B, Lal S, Kaplan S, Softness B, Greenberg E, et al. Diabetes mellitus promotes periodontal destruction in children. J Clin Periodontol. 2007;34(4):294–8.

    Article  PubMed  Google Scholar 

  65. Deshpande K, Jain A, Sharma R, Prashar S, Jain R. Diabetes and periodontitis. J Indian Soc Periodontol. 2010;14(4):207–12.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Chapple IL, Genco R, Working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol. 2013;84(4 Suppl):S106–12.

    PubMed  Google Scholar 

  67. Tervonen T, Karjalainen K, Knuuttila M, Huumonen S. Alveolar bone loss in type 1 diabetic subjects. J Clin Periodontol. 2000;27(8):567–71.

    Article  CAS  PubMed  Google Scholar 

  68. Kim JH, Lee DE, Choi SH, Cha JH, Bak EJ, Yoo YJ. Diabetic characteristics and alveolar bone loss in streptozotocin- and streptozotocin-nicotinamide-treated rats with periodontitis. J Periodontal Res. 2014;49(6):792–800.

    Article  CAS  PubMed  Google Scholar 

  69. Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, et al. Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2 years. J Periodontol. 1998;69(1):76–83.

    Article  CAS  PubMed  Google Scholar 

  70. Suzuki K, Kurose T, Takizawa M, Maruyama M, Ushikawa K, Kikuyama M, et al. Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density. Diabetes Res Clin Pract. 2005;68(2):117–25.

    Article  CAS  PubMed  Google Scholar 

  71. Suzuki K, Ishida H, Takeshita N, Taguchi Y, Sugimoto C, Nosaka K, et al. Circulating levels of tartrate-resistant acid phosphatase in rat models of non-insulin-dependent diabetes mellitus. J Diabetes Complications. 1998;12(3):176–80.

    Article  CAS  PubMed  Google Scholar 

  72. Silva JA, Lopes Ferrucci D, Peroni LA, de Paula Ishi E, Rossa-Junior C, Carvalho HF, et al. Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis. Cells Tissues Organs. 2012;196(2):137–50.

    Article  CAS  PubMed  Google Scholar 

  73. Graves DT, Naguib G, Lu H, Leone C, Hsue H, Krall E. Inflammation is more persistent in type 1 diabetic mice. J Dent Res. 2005;84:324–8.

    Article  CAS  PubMed  Google Scholar 

  74. Kayal RA, Tsatsas D, Bauer MA, Allen B, Al-Sebaei MO, Kakar S, et al. Diminished bone formation during diabetic fracture healing is related to the premature resorption of cartilage associated with increased osteoclast activity. J Bone Miner Res. 2007;22(4):560–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet. 2005;366(9502):2058–61.

    Article  CAS  PubMed  Google Scholar 

  76. Alblowi J, Kayal RA, Siqueria M, McKenzie E, Krothapalli N, McLean J, et al. High levels of tumor necrosis factor-alpha contribute to accelerated loss of cartilage in diabetic fracture healing. Am J Pathol. 2009;175(4):1574–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Graves DT, Liu R, Alikhani M, Al-Mashat H, Trackman PC. Diabetes-enhanced inflammation and apoptosis—impact on periodontal pathology. J Dent Res. 2006;85(1):15–21.

    Article  CAS  PubMed  Google Scholar 

  78. Silva JA, Ferrucci DL, Peroni LA, Abrahao PG, Salamene AF, Rossa-Junior C, et al. Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes. J Cell Physiol. 2012;227(6):2441–50.

    Article  CAS  PubMed  Google Scholar 

  79. Duarte PM, de Oliveira MC, Tambeli CH, Parada CA, Casati MZ, Nociti Jr FH. Overexpression of interleukin-1beta and interleukin-6 may play an important role in periodontal breakdown in type 2 diabetic patients. J Periodontal Res. 2007;42(4):377–81.

    Article  CAS  PubMed  Google Scholar 

  80. Bastos AS, Graves DT, Loureiro AP, Rossa Junior C, Abdalla DS, Faulin TD, et al. Lipid peroxidation is associated with the severity of periodontal disease and local inflammatory markers in patients with type 2 diabetes. J Clin Endocrinol Metab. 2012;97(8):E1353–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Drosatos-Tampakaki Z, Drosatos K, Siegelin Y, Gong S, Khan S, Van Dyke T, et al. Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it. J Bone Miner Res. 2014;29(5):1183–95.

    Article  CAS  PubMed  Google Scholar 

  82. Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol. 2007;179(10):7021–9.

    Article  CAS  PubMed  Google Scholar 

  83. Gyurko R, Van Dyke TE. The role of polyunsaturated omega-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1) in bone preservation. Crit Rev Immunol. 2014;34(4):347–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Omori K, Ohira T, Uchida Y, Ayilavarapu S, Batista Jr EL, Yagi M, et al. Priming of neutrophil oxidative burst in diabetes requires preassembly of the NADPH oxidase. J Leukoc Biol. 2008;84(1):292–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Thomas B, Ramesh A, Suresh S, Prasad BR. A comparative evaluation of antioxidant enzymes and selenium in the serum of periodontitis patients with diabetes mellitus type 2. Contemp Clin Dent. 2013;4(2):176–80.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR. Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest. 1990;85(3):632–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Collin HL, Sorsa T, Meurman JH, Niskanen L, Salo T, Ronka H, et al. Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus. J Periodontal Res. 2000;35(5):259–65.

    Article  CAS  PubMed  Google Scholar 

  88. Ha H, Kwak HB, Lee SW, Jin HM, Kim HM, Kim HH, et al. Reactive oxygen species mediate RANK signaling in osteoclasts. Exp Cell Res. 2004;301(2):119–27.

    Article  CAS  PubMed  Google Scholar 

  89. Catalfamo DL, Britten TM, Storch DL, Calderon NL, Sorenson HL, Wallet SM. Hyperglycemia induced and intrinsic alterations in type 2 diabetes-derived osteoclast function. Oral Dis. 2013;19(3):303–12.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Miyata T, Kawai R, Taketomi S, Sprague SM. Possible involvement of advanced glycation end-products in bone resorption. Nephrol Dial Transplant. 1996;11 Suppl 5:54–7.

    Article  CAS  PubMed  Google Scholar 

  91. Ding KH, Wang ZZ, Hamrick MW, Deng ZB, Zhou L, Kang B, et al. Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss. Biochem Biophys Res Commun. 2006;340(4):1091–7.

    Article  CAS  PubMed  Google Scholar 

  92. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318(20):1315–21.

    Article  CAS  PubMed  Google Scholar 

  93. Zizzi A, Tirabassi G, Aspriello SD, Piemontese M, Rubini C, Lucarini G. Gingival advanced glycation end-products in diabetes mellitus-associated chronic periodontitis: an immunohistochemical study. J Periodontal Res. 2013;48(3):293–301.

    Article  CAS  PubMed  Google Scholar 

  94. Mealey BL, Oates TW. Diabetes mellitus and periodontal diseases. J Periodontol. 2006;77(8):1289–303.

    Article  CAS  PubMed  Google Scholar 

  95. Lamster IB. Diabetes and oral health. What’s their relationship? Diabetes Self Manag. 2012;29(3):30, 32–4.

    Google Scholar 

  96. Lappin DF, Eapen B, Robertson D, Young J, Hodge PJ. Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus. J Clin Periodontol. 2009;36(8):634–41.

    Article  CAS  PubMed  Google Scholar 

  97. Mahamed DA, Marleau A, Alnaeeli M, Singh B, Zhang X, Penninger JM, et al. G(-) anaerobes-reactive CD4+ T-cells trigger RANKL-mediated enhanced alveolar bone loss in diabetic NOD mice. Diabetes. 2005;54(5):1477–86.

    Article  CAS  PubMed  Google Scholar 

  98. Santos VR, Lima JA, Goncalves TE, Bastos MF, Figueiredo LC, Shibli JA, et al. Receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio in sites of chronic periodontitis of subjects with poorly and well-controlled type 2 diabetes. J Periodontol. 2010;81(10):1455–65.

    Article  CAS  PubMed  Google Scholar 

  99. Lu H, Kraut D, Gerstenfeld L, Graves D. Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation. Endocrinology. 2003;144:346–52.

    Article  CAS  PubMed  Google Scholar 

  100. Hamann C, Goettsch C, Mettelsiefen J, Henkenjohann V, Rauner M, Hempel U, et al. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Endocrinol Metab. 2011;301(6):E1220–8.

    Article  CAS  PubMed  Google Scholar 

  101. Weinberg E, Maymon T, Moses O, Weinreb M. Streptozotocin-induced diabetes in rats diminishes the size of the osteoprogenitor pool in bone marrow. Diabetes Res Clin Pract. 2014;103(1):35–41.

    Article  CAS  PubMed  Google Scholar 

  102. Chang J, Liu F, Lee M, Wu B, Ting K, Zara JN, et al. NF-kappaB inhibits osteogenic differentiation of mesenchymal stem cells by promoting beta-catenin degradation. Proc Natl Acad Sci U S A. 2013;110(23):9469–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Invest. 2011;41(12):1361–6.

    Article  CAS  PubMed  Google Scholar 

  104. Chang J, Wang Z, Tang E, Fan Z, McCauley L, Franceschi R, et al. Inhibition of osteoblastic bone formation by nuclear factor-kappaB. Nat Med. 2009;15(6):682–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Pacifici R. The immune system and bone. Arch Biochem Biophys. 2010;503(1):41–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, et al. Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology. 2000;141(11):3956–64.

    CAS  PubMed  Google Scholar 

  107. Lencel P, Delplace S, Hardouin P, Magne D. TNF-alpha stimulates alkaline phosphatase and mineralization through PPARgamma inhibition in human osteoblasts. Bone. 2011;48(2):242–9.

    Article  CAS  PubMed  Google Scholar 

  108. Guo R, Yamashita M, Zhang Q, Zhou Q, Chen D, Reynolds DG, et al. Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins. J Biol Chem. 2008;283(34):23084–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  109. Lalla E, Lamster IB, Schmidt AM. Enhanced interaction of advanced glycation end products with their cellular receptor RAGE: implications for the pathogenesis of accelerated periodontal disease in diabetes. Ann Periodontol. 1998;3(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  110. Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, et al. Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone. 2007;40(2):345–53.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC. A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes. 2003;52(6):1502–10.

    Article  CAS  PubMed  Google Scholar 

  112. Liu R, Bal HS, Desta T, Behl Y, Graves DT. Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol. 2006;168(3):757–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  113. Gilbert LC, Rubin J, Nanes MS. The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation independently of apoptosis. Am J Physiol Endocrinol Metab. 2005;288(5):E1011–8.

    Article  CAS  PubMed  Google Scholar 

  114. Lu X, Beck Jr GR, Gilbert LC, Camalier CE, Bateman NW, Hood BL, et al. Identification of the homeobox protein Prx1 (MHox, Prrx-1) as a regulator of osterix expression and mediator of tumor necrosis factor alpha action in osteoblast differentiation. J Bone Miner Res. 2011;26(1):209–19.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  115. Stolzing A, Sellers D, Llewelyn O, Scutt A. Diabetes induced changes in rat mesenchymal stem cells. Cells Tissues Organs. 2010;191(6):453–65.

    Article  CAS  PubMed  Google Scholar 

  116. Kume S, Kato S, Yamagishi S, Inagaki Y, Ueda S, Arima N, et al. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone. J Bone Miner Res. 2005;20(9):1647–58.

    Article  CAS  PubMed  Google Scholar 

  117. Notsu M, Yamaguchi T, Okazaki K, Tanaka K, Ogawa N, Kanazawa I, et al. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-beta expression and secretion. Endocrinology. 2014;155(7):2402–10.

    Article  PubMed  CAS  Google Scholar 

  118. Shin L, Peterson DA. Impaired therapeutic capacity of autologous stem cells in a model of type 2 diabetes. Stem Cells Transl Med. 2012;1(2):125–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Ponugoti B, Dong G, Graves DT. Role of forkhead transcription factors in diabetes-induced oxidative stress. Exp Diabetes Res. 2012;2012:939751.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  120. Graves DT, Liu R, Oates TW. Diabetes-enhanced inflammation and apoptosis: impact on periodontal pathosis. Periodontol 2000. 2007;45:128–37.

    Article  PubMed  Google Scholar 

  121. Chowdhury I, Tharakan B, Bhat GK. Caspases—an update. Comp Biochem Physiol B Biochem Mol Biol. 2008;151(1):10–27.

    Article  PubMed  CAS  Google Scholar 

  122. Al-Mashat HA, Kandru S, Liu R, Behl Y, Desta T, Graves DT. Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing. Diabetes. 2006;55(2):487–95.

    Article  CAS  PubMed  Google Scholar 

  123. Alikhani M, Alikhani Z, He H, Liu R, Popek BI, Graves DT. Lipopolysaccharides indirectly stimulate apoptosis and global induction of apoptotic genes in fibroblasts. J Biol Chem. 2003;278(52):52901–8.

    Article  CAS  PubMed  Google Scholar 

  124. Alikhani M, Alikhani Z, Graves DT. FOXO1 functions as a master switch that regulates gene expression necessary for tumor necrosis factor-induced fibroblast apoptosis. J Biol Chem. 2005;280(13):12096–102.

    Article  CAS  PubMed  Google Scholar 

  125. Fu YW, He HB, Ou JG. Osteoblast apoptosis in experimental diabetic periodontitis in rats. Hua Xi Kou Qiang Yi Xue Za Zhi. 2009;27(3):252–5, 259.

    Google Scholar 

  126. Behl Y, Siqueira M, Ortiz J, Li J, Desta T, Faibish D, et al. Activation of the acquired immune response reduces coupled bone formation in response to a periodontal pathogen. J Immunol. 2008;181(12):8711–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  127. Hein G, Weiss C, Lehmann G, Niwa T, Stein G, Franke S. Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings. Ann Rheum Dis. 2006;65(1):101–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  128. Fu YW, He HB. Apoptosis of periodontium cells in streptozototocin- and ligature-induced experimental diabetic periodontitis in rats. Acta Odontol Scand. 2013;71(5):1206–15.

    Article  PubMed  Google Scholar 

  129. Ohnishi T, Bandow K, Kakimoto K, Machigashira M, Matsuyama T, Matsuguchi T. Oxidative stress causes alveolar bone loss in metabolic syndrome model mice with type 2 diabetes. J Periodontal Res. 2009;44(1):43–51.

    Article  CAS  PubMed  Google Scholar 

  130. Wang GW, Klein JB, Kang YJ. Metallothionein inhibits doxorubicin-induced mitochondrial cytochrome c release and caspase-3 activation in cardiomyocytes. J Pharmacol Exp Ther. 2001;298(2):461–8.

    CAS  PubMed  Google Scholar 

  131. Isaka J, Ohazama A, Kobayashi M, Nagashima C, Takiguchi T, Kawasaki H, et al. Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol. 2001;72(3):314–23.

    Article  CAS  PubMed  Google Scholar 

  132. He H, Liu R, Desta T, Leone C, Gerstenfeld LC, Graves DT. Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. Endocrinology. 2004;145(1):447–52.

    Article  CAS  PubMed  Google Scholar 

  133. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011;7(12):738–48.

    Article  CAS  PubMed  Google Scholar 

  134. Walsh NC, Reinwald S, Manning CA, Condon KW, Iwata K, Burr DB, et al. Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis. J Bone Miner Res. 2009;24(9):1572–85.

    Article  CAS  PubMed  Google Scholar 

  135. Walsh NC, Gravallese EM. Bone remodeling in rheumatic disease: a question of balance. Immunol Rev. 2010;233(1):301–12.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, China

    E. Xiao

  2. Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    E. Xiao, Yingying Wu & Dana T. Graves D.D.S., D.M.Sc.

  3. State Key Laboratory of Oral Disease, West China School of Stomatology Sichuan University, Chengdu, Sichuan, 610041, China

    Yingying Wu

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  1. E. Xiao
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  2. Yingying Wu
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  3. Dana T. Graves D.D.S., D.M.Sc.
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Correspondence to Dana T. Graves D.D.S., D.M.Sc. .

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Editors and Affiliations

  1. Departments of Orthopedic Surgery, Physiology and Pharmacology, Center for Diabetes and Endocrine Research; University of Toledo, Toledo, Ohio, USA

    Beata Lecka-Czernik

  2. Departments of Pediatrics, Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA

    John L. Fowlkes

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Xiao, E., Wu, Y., Graves, D.T. (2016). Impact of Diabetes on Periodontal Disease. In: Lecka-Czernik, B., Fowlkes, J. (eds) Diabetic Bone Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-16402-1_5

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  • DOI: https://doi.org/10.1007/978-3-319-16402-1_5

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