Osteoimmunological Aspects of Periodontal Diseases

  • Kristina Bertl
  • Peter Pietschmann
  • Andreas Stavropoulos
Chapter
First Online:

Abstract

Osteoimmunology describes the cross-talk of cells of the musculoskeletal and the immune system during the pathogenesis of various diseases; among the most prevalent ones is periodontitis, a chronic infectious inflammatory disease of the tooth-supporting structures, i.e., the periodontium consisting of the gingiva, alveolar bone, periodontal ligament, and root cementum. Periodontal disease is initiated by oral pathogens that accumulate at the gingival margin of the teeth and thereby trigger a response of the innate and adaptive immunity. In contrast to other osteoimmunological disorders (e.g., osteoporosis, rheumatoid arthritis), the immune system plays a two-sided role in the pathogenesis of periodontitis: it controls the infection and protects the organism from bacterial invasion but also propagates the destruction of the soft and hard tissues surrounding the tooth. Periodontitis, if left untreated, finally results in tooth loss.

Keywords

Alveolar Bone Chronic Periodontitis Periodontal Tissue Gingival Crevicular Fluid Periodontal Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

AgP

Aggressive periodontitis

C3

Complement component 3

CP

Chronic periodontitis

IFN

Interferon

Ig

Immunoglobulin

IL

Interleukin

iNOS

Inducible NO-synthases

LPS

Lipopolysaccharide

M-CSF

Macrophage colony-stimulating factor

MMP

Matrix metalloproteinases

NO

Nitric oxide

OPG

Osteoprotegerin

RANK

Receptor activator of NF-kB

RANKL

Receptor activator of nuclear factor “kappa-light-chain-enhancer” of the activated B cell ligand

TGF

Transforming growth factor

Th

T helper cells

TIMP

Tissue inhibitors of metalloproteinase

TLR

Toll-like receptors

TNF

Tumor necrosis factor

Treg

Regulatory T cells

This is a preview of subscription content, log in to check access.

References

  1. Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793PubMedCrossRefGoogle Scholar
  2. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511PubMedCrossRefGoogle Scholar
  3. Alayan J, Ivanovski S, Gemmell E, Ford P, Hamlet S, Farah CS (2006) Deficiency of iNOS contributes to Porphyromonas gingivalis-induced tissue damage. Oral Microbiol Immunol 21:360–365PubMedCrossRefGoogle Scholar
  4. Anderson DM, Maraskovsky E, Billingsley WL et al (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390:175–179PubMedCrossRefGoogle Scholar
  5. Appay V, van Lier RA, Sallusto F, Roederer M (2008) Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A 73:975–983PubMedCrossRefGoogle Scholar
  6. Arabacı T, Kermen E, Özkanlar S et al (2015) Therapeutic effects of melatonin on alveolar bone resorption after experimental periodontitis in rats: a biochemical and immunohistochemical study. J Periodontol 86:874–881PubMedCrossRefGoogle Scholar
  7. Araújo AA, Lopes de Souza G, Souza TO et al (2013a) Olmesartan decreases IL-1β and TNF-α levels; downregulates MMP-2, MMP-9, COX-2, and RANKL; and upregulates OPG in experimental periodontitis. Naunyn Schmiedebergs Arch Pharmacol 386:875–884PubMedCrossRefGoogle Scholar
  8. Araújo AA, Souza TO, Moura LM et al (2013b) Effect of telmisartan on levels of IL-1, TNF-α, down-regulated COX-2, MMP-2, MMP-9 and RANKL/RANK in an experimental periodontitis model. J Clin Periodontol 40:1104–1111PubMedPubMedCentralCrossRefGoogle Scholar
  9. Araújo AA, Varela H, Brito GA et al (2014) Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model. PLoS One 9, e96750PubMedPubMedCentralCrossRefGoogle Scholar
  10. Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4:1–6PubMedCrossRefGoogle Scholar
  11. Armitage GC, Cullinan MP (2010) Comparison of the clinical features of chronic and aggressive periodontitis. Periodontol 2000 53:12–27PubMedCrossRefGoogle Scholar
  12. Aurer A, Aleksic J, Ivic-Kardum M, Aurer J, Culo F (2001) Nitric oxide synthesis is decreased in periodontitis. J Clin Periodontol 28:565–568PubMedCrossRefGoogle Scholar
  13. Baker PJ, Dixon M, Evans RT, Dufour L, Johnson E, Roopenian DC (1999) CD4(+) T cells and the proinflammatory cytokines gamma interferon and interleukin-6 contribute to alveolar bone loss in mice. Infect Immun 67:2804–2809PubMedPubMedCentralGoogle Scholar
  14. Baker PJ, Boutaugh NR, Tiffany M, Roopenian DC (2009) B cell IgD deletion prevents Alveolar bone loss following murine oral infection. Interdiscip Perspect Infect Dis 2009:864359PubMedPubMedCentralGoogle Scholar
  15. Banu S, Jabir NR, Mohan R et al (2015) Correlation of Toll-like receptor 4, interleukin-18, transaminases, and uric acid in patients with chronic periodontitis and healthy adults. J Periodontol 86:431–439PubMedCrossRefGoogle Scholar
  16. Bar-Shavit Z (2008) Taking a toll on the bones: regulation of bone metabolism by innate immune regulators. Autoimmunity 41:195–203PubMedCrossRefGoogle Scholar
  17. Bartold PM, Cantley MD, Haynes DR (2010) Mechanisms and control of pathologic bone loss in periodontitis. Periodontol 2000 53:55–69PubMedCrossRefGoogle Scholar
  18. Beklen A, Sorsa T, Konttinen YT (2009) Toll-like receptors 2 and 5 in human gingival epithelial cells co-operate with T-cell cytokine interleukin-17. Oral Microbiol Immunol 24:38–42PubMedCrossRefGoogle Scholar
  19. Belibasakis GN, Bostanci N, Hashim A et al (2007) Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains. Microb Pathog 43:46–53PubMedCrossRefGoogle Scholar
  20. Bertl K, Schoiber A, Haririan H et al (2013) Non-surgical periodontal therapy influences salivary melatonin levels. Clin Oral Investig 17:1219–1225PubMedCrossRefGoogle Scholar
  21. Bertl K, Bruckmann C, Isberg PE, Klinge B, Gotfredsen K, Stavropoulos A (2015) Hyaluronan in non-surgical and surgical periodontal therapy: a systematic review. J Clin Periodontol 42:236–246PubMedCrossRefGoogle Scholar
  22. Bickel M (1993) The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 64:456–460PubMedGoogle Scholar
  23. Bloemen V, Schoenmaker T, de Vries TJ, Everts V (2010) Direct cell-cell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis. J Cell Physiol 222:565–573PubMedGoogle Scholar
  24. Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRefGoogle Scholar
  25. Bradshaw DJ, Marsh PD, Watson GK, Allison C (1998) Role of Fusobacterium nucleatum and coaggregation in anaerobe survival in planktonic and biofilm oral microbial communities during aeration. Infect Immun 66:4729–4732PubMedPubMedCentralGoogle Scholar
  26. Brennan PA, Thomas GJ, Langdon JD (2003) The role of nitric oxide in oral diseases. Arch Oral Biol 48:93–100PubMedCrossRefGoogle Scholar
  27. Brook I (2003) Microbiology and management of periodontal infections. Gen Dent 51:424–428PubMedGoogle Scholar
  28. Brunetti G, Colucci S, Pignataro P et al (2005) T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients. J Periodontol 76:1675–1680PubMedCrossRefGoogle Scholar
  29. Cardoso CR, Garlet GP, Moreira AP, Junior WM, Rossi MA, Silva JS (2008) Characterization of CD4 + CD25+ natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis. J Leukoc Biol 84:311–318PubMedCrossRefGoogle Scholar
  30. Castro ML, Franco GC, Branco-de-Almeida LS et al (2016) Down-Regulation of protease activated receptor 2, interleukin-17 and other pro-inflammatory genes by subantimicrobial doxycycline dose in a rat periodontitis model. J Periodontol 87:203–210Google Scholar
  31. Chakravarti A, Raquil MA, Tessier P, Poubelle PE (2009) Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption. Blood 114:1633–1644PubMedCrossRefGoogle Scholar
  32. Chalifour A, Jeannin P, Gauchat JF et al (2004) Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood 104:1778–1783PubMedCrossRefGoogle Scholar
  33. Chang PC, Chong LY, Tsai SC, Lim LP (2014) Aminoguanidine inhibits the AGE-RAGE axis to modulate the induction of periodontitis but has limited effects on the progression and recovery of experimental periodontitis: a preliminary study. J Periodontol 85:729–739PubMedCrossRefGoogle Scholar
  34. Cheng WC, Hughes FJ, Taams LS (2014) The presence, function and regulation of IL-17 and Th17 cells in periodontitis. J Clin Periodontol 41:541–549PubMedCrossRefGoogle Scholar
  35. Claudino M, Trombone AP, Cardoso CR et al (2008) The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome. J Leukoc Biol 84:1565–1573PubMedCrossRefGoogle Scholar
  36. Claudino M, Garlet TP, Cardoso CR et al (2010) Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice. Eur J Oral Sci 118:19–28PubMedCrossRefGoogle Scholar
  37. Cochran DL (2008) Inflammation and bone loss in periodontal disease. J Periodontol 79:1569–1576PubMedCrossRefGoogle Scholar
  38. Cronstein BN (2007) Interleukin-6--a key mediator of systemic and local symptoms in rheumatoid arthritis. Bull NYU Hosp Jt Dis 65(Suppl 1):S11–S15PubMedGoogle Scholar
  39. Crotti T, Smith MD, Hirsch R et al (2003) Receptor activator NF kappaB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis. J Periodontal Res 38:380–387PubMedCrossRefGoogle Scholar
  40. Daghigh F, Borghaei RC, Thornton RD, Bee JH (2002) Human gingival fibroblasts produce nitric oxide in response to proinflammatory cytokines. J Periodontol 73:392–400PubMedCrossRefGoogle Scholar
  41. Damgaard C, Holmstrup P, Van Dyke TE, Nielsen CH (2015) The complement system and its role in the pathogenesis of periodontitis: current concepts. J Periodontal Res 50:283–293PubMedCrossRefGoogle Scholar
  42. De Almeida J, Ervolino E, Bonfietti LH et al (2015) Adjuvant therapy with sodium alendronate for the treatment of experimental periodontitis in rats. J Periodontol 86:1166–1175PubMedCrossRefGoogle Scholar
  43. de Vries TJ, Yousovich J, Schoenmaker T, Scheres N, Everts V (2016) Tumor necrosis factor-α antagonist infliximab inhibits osteoclast formation of peripheral blood mononuclear cells but does not affect periodontal ligament fibroblast-mediated osteoclast formation. J Periodontal Res 51:186–195Google Scholar
  44. de Waal Malefyt R, Figdor CG, Huijbens R et al (1993) Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 151:6370–6381PubMedGoogle Scholar
  45. Deas DE, Mealey BL (2010) Response of chronic and aggressive periodontitis to treatment. Periodontol 2000 53:154–166PubMedCrossRefGoogle Scholar
  46. Di Paola R, Marzocco S, Mazzon E et al (2004) Effect of aminoguanidine in ligature-induced periodontitis in rats. J Dent Res 83:343–348PubMedCrossRefGoogle Scholar
  47. Di Paola R, Mazzon E, Muià C et al (2007) Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an experimental model of periodontitis in rats. Br J Pharmacol 150:286–297PubMedPubMedCentralCrossRefGoogle Scholar
  48. Donati M, Liljenberg B, Zitzmann NU, Berglundh T (2009) B-1a cells and plasma cells in periodontitis lesions. J Periodontal Res 44:683–688PubMedCrossRefGoogle Scholar
  49. Duarte PM, de Oliveira MC, Tambeli CH, Parada CA, Casati MZ, Nociti FH (2007) Overexpression of interleukin-1beta and interleukin-6 may play an important role in periodontal breakdown in type 2 diabetic patients. J Periodontal Res 42:377–381PubMedCrossRefGoogle Scholar
  50. Ebersole JL, Schuster JL, Stevens J et al (2013) Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health. J Clin Immunol 33:271–279PubMedCrossRefGoogle Scholar
  51. Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ (2012) Update of the case definitions for population-based surveillance of periodontitis. J Periodontol 83:1449–1454PubMedCrossRefGoogle Scholar
  52. Ertugrul AS, Sahin H, Dikilitas A, Alpaslan N, Bozoglan A (2013) Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. J Periodontal Res 48:44–51PubMedCrossRefGoogle Scholar
  53. Fajardo ME, Rocha ML, Sánchez-Marin FJ, Espinosa-Chávez EJ (2010) Effect of atorvastatin on chronic periodontitis: a randomized pilot study. J Clin Periodontol 37:1016–1022PubMedCrossRefGoogle Scholar
  54. Faust J, Lacey DL, Hunt P et al (1999) Osteoclast markers accumulate on cells developing from human peripheral blood mononuclear precursors. J Cell Biochem 72:67–80PubMedCrossRefGoogle Scholar
  55. Ferrari-Lacraz S, Ferrari S (2011) Do RANKL inhibitors (denosumab) affect inflammation and immunity? Osteoporos Int 22:435–46Google Scholar
  56. Flemmig TF (1999) Periodontitis. Ann Periodontol 4:32–38PubMedCrossRefGoogle Scholar
  57. Ford PJ, Gamonal J, Seymour GJ (2010) Immunological differences and similarities between chronic periodontitis and aggressive periodontitis. Periodontol 2000 53:111–123PubMedCrossRefGoogle Scholar
  58. Foster JS, Kolenbrander PE (2004) Development of a multispecies oral bacterial community in a saliva-conditioned flow cell. Appl Environ Microbiol 70:4340–4348PubMedPubMedCentralCrossRefGoogle Scholar
  59. Fukada SY, Silva TA, Saconato IF et al (2008) iNOS-derived nitric oxide modulates infection-stimulated bone loss. J Dent Res 87:1155–1159PubMedCrossRefGoogle Scholar
  60. Fuller K, Wong B, Fox S, Choi Y, Chambers TJ (1998) TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med 188:997–1001PubMedPubMedCentralCrossRefGoogle Scholar
  61. Furlaneto FA, Nunes NL, Oliveira Filho IL et al (2014) Effects of locally administered tiludronic acid on experimental periodontitis in rats. J Periodontol 85:1291–1301PubMedCrossRefGoogle Scholar
  62. Gaffen SL, Hajishengallis G (2008) A new inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res 87:817–828PubMedPubMedCentralCrossRefGoogle Scholar
  63. Gamonal J, Acevedo A, Bascones A, Jorge O, Silva A (2000) Levels of interleukin-1 beta, −8, and −10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment. J Periodontol 71:1535–1545PubMedCrossRefGoogle Scholar
  64. Gao Y, Grassi F, Ryan MR et al (2007) IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen-driven T cell activation. J Clin Invest 117:122–132PubMedCrossRefGoogle Scholar
  65. Garcia MN, Hildebolt CF, Miley DD et al (2011) One-year effects of vitamin D and calcium supplementation on chronic periodontitis. J Periodontol 82:25–32PubMedCrossRefGoogle Scholar
  66. Garlet GP (2010) Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res 89:1349–1363PubMedCrossRefGoogle Scholar
  67. Garlet GP, Martins WJ, Ferreira BR, Milanezi CM, Silva JS (2003) Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. J Periodontal Res 38:210–217PubMedCrossRefGoogle Scholar
  68. Garlet GP, Martins WJ, Fonseca BA, Ferreira BR, Silva JS (2004) Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. J Clin Periodontol 31:671–679PubMedCrossRefGoogle Scholar
  69. Garlet GP, Cardoso CR, Silva TA et al (2006) Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors. Oral Microbiol Immunol 21:12–20PubMedCrossRefGoogle Scholar
  70. Garlet GP, Cardoso CR, Campanelli AP et al (2007) The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction. Clin Exp Immunol 147:128–138PubMedPubMedCentralGoogle Scholar
  71. Garlet GP, Cardoso CR, Campanelli AP et al (2008) The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice. Microbes Infect 10:489–496PubMedCrossRefGoogle Scholar
  72. Gemmell E, Seymour GJ (1994) Cytokines and T cell switching. Crit Rev Oral Biol Med 5:249–279PubMedGoogle Scholar
  73. Genco RJ, Borgnakke WS (2013) Risk factors for periodontal disease. Periodontol 2000 62:59–94PubMedCrossRefGoogle Scholar
  74. Giannobile WV (2008) Host-response therapeutics for periodontal diseases. J Periodontol 79:1592–1600PubMedPubMedCentralCrossRefGoogle Scholar
  75. Gonçalves DC, Evangelista RC, da Silva RR et al (2014) Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats. Exp Biol Med (Maywood) 239:442–453CrossRefGoogle Scholar
  76. Gonzales JR (2015) T- and B-cell subsets in periodontitis. Periodontol 2000 69:181–200PubMedCrossRefGoogle Scholar
  77. Graves D (2008) Cytokines that promote periodontal tissue destruction. J Periodontol 79:1585–1591PubMedCrossRefGoogle Scholar
  78. Graves DT, Cochran D (2003) The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 74:391–401PubMedCrossRefGoogle Scholar
  79. Graves DT, Li J, Cochran DL (2011) Inflammation and uncoupling as mechanisms of periodontal bone loss. J Dent Res 90:143–153PubMedPubMedCentralCrossRefGoogle Scholar
  80. Guentsch A, Puklo M, Preshaw PM et al (2009) Neutrophils in chronic and aggressive periodontitis in interaction with Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. J Periodontal Res 44:368–377PubMedPubMedCentralCrossRefGoogle Scholar
  81. Gursoy UK, Könönen E, Uitto VJ et al (2009) Salivary interleukin-1beta concentration and the presence of multiple pathogens in periodontitis. J Clin Periodontol 36:922–927PubMedCrossRefGoogle Scholar
  82. Gursoy UK, Könönen E, Huumonen S et al (2013) Salivary type I collagen degradation end-products and related matrix metalloproteinases in periodontitis. J Clin Periodontol 40:18–25PubMedCrossRefGoogle Scholar
  83. Gustafsson A, Ito H, Asman B, Bergstrom K (2006) Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis. J Clin Periodontol 33:126–129PubMedCrossRefGoogle Scholar
  84. Hajishengallis G (2014) Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol 35:3–11PubMedCrossRefGoogle Scholar
  85. Hajishengallis G, Lamont RJ (2012) Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 27:409–419PubMedPubMedCentralCrossRefGoogle Scholar
  86. Hajishengallis G, Liang S, Payne MA et al (2011) Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 10:497–506PubMedPubMedCentralCrossRefGoogle Scholar
  87. Hajishengallis G, Darveau RP, Curtis MA (2012) The keystone-pathogen hypothesis. Nat Rev Microbiol 10:717–725PubMedPubMedCentralCrossRefGoogle Scholar
  88. Han X, Kawai T, Eastcott JW, Taubman MA (2006) Bacterial-responsive B lymphocytes induce periodontal bone resorption. J Immunol 176:625–631PubMedCrossRefGoogle Scholar
  89. Han X, Lin X, Seliger AR, Eastcott J, Kawai T, Taubman MA (2009) Expression of receptor activator of nuclear factor-kappaB ligand by B cells in response to oral bacteria. Oral Microbiol Immunol 24:190–196PubMedPubMedCentralCrossRefGoogle Scholar
  90. Hao L, Chen J, Zhu Z et al (2015) Odanacatib, a cathepsin K-Specific inhibitor, inhibits inflammation and bone loss caused by periodontal diseases. J Periodontol 86:972–983PubMedPubMedCentralCrossRefGoogle Scholar
  91. Hasturk H, Kantarci A, Goguet-Surmenian E et al (2007) Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 179:7021–7029PubMedCrossRefGoogle Scholar
  92. Hayami T, Kapila YL, Kapila S (2008) MMP-1 (collagenase-1) and MMP-13 (collagenase-3) differentially regulate markers of osteoblastic differentiation in osteogenic cells. Matrix Biol 27:682–692PubMedPubMedCentralCrossRefGoogle Scholar
  93. Himani GS, Prabhuji ML, Karthikeyan BV (2014) Gingival crevicular fluid and interleukin-23 concentration in systemically healthy subjects: their relationship in periodontal health and disease. J Periodontal Res 49:237–245PubMedCrossRefGoogle Scholar
  94. Holt SC, Ebersole JL (2005) Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000 38:72–122PubMedCrossRefGoogle Scholar
  95. Holtfreter B, Kocher T, Hoffmann T, Desvarieux M, Micheelis W (2010) Prevalence of periodontal disease and treatment demands based on a German dental survey (DMS IV). J Clin Periodontol 37:211–219PubMedCrossRefGoogle Scholar
  96. Honda T, Domon H, Okui T, Kajita K, Amanuma R, Yamazaki K (2006) Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions. Clin Exp Immunol 144:35–40PubMedCentralCrossRefPubMedGoogle Scholar
  97. Ihn H, Yamane K, Asano Y, Kubo M, Tamaki K (2002) IL-4 up-regulates the expression of tissue inhibitor of metalloproteinase-2 in dermal fibroblasts via the p38 mitogen-activated protein kinase dependent pathway. J Immunol 168:1895–1902PubMedCrossRefGoogle Scholar
  98. Irwin CR, Myrillas TT (1998) The role of IL-6 in the pathogenesis of periodontal disease. Oral Dis 4:43–47PubMedCrossRefGoogle Scholar
  99. Isaza-Guzmán DM, Cardona-Vélez N, Gaviria-Correa DE, Martínez-Pabón MC, Castaño-Granada MC, Tobón-Arroyave SI (2015) Association study between salivary levels of interferon (IFN)-gamma, interleukin (IL)-17, IL-21, and IL-22 with chronic periodontitis. Arch Oral Biol 60:91–99PubMedCrossRefGoogle Scholar
  100. Jarnicki AG, Fallon PG (2003) T helper type-2 cytokine responses: potential therapeutic targets. Curr Opin Pharmacol 3:449–455PubMedCrossRefGoogle Scholar
  101. Jenkinson HF, Lamont RJ (2005) Oral microbial communities in sickness and in health. Trends Microbiol 13:589–595PubMedCrossRefGoogle Scholar
  102. Ji JD, Park-Min KH, Shen Z et al (2009) Inhibition of RANK expression and osteoclastogenesis by TLRs and IFN-gamma in human osteoclast precursors. J Immunol 183:7223–7233PubMedPubMedCentralCrossRefGoogle Scholar
  103. Jin Q, Cirelli JA, Park CH et al (2007) RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis. J Periodontol 78:1300–1308PubMedPubMedCentralCrossRefGoogle Scholar
  104. Johnson RB, Serio FG (2007) The contribution of interleukin-13 and −15 to the cytokine network within normal and diseased gingiva. J Periodontol 78:691–695PubMedCrossRefGoogle Scholar
  105. Joseph J, Kapila YL, Hayami T, Kapila S (2010) Disease-associated extracellular matrix suppresses osteoblastic differentiation of human periodontal ligament cells via MMP-1. Calcif Tissue Int 86:154–162PubMedCrossRefGoogle Scholar
  106. Jovanovic DV, Di Battista JA, Martel-Pelletier J et al (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160:3513–3521PubMedGoogle Scholar
  107. Kadono H, Kido J, Kataoka M, Yamauchi N, Nagata T (1999) Inhibition of osteoblastic cell differentiation by lipopolysaccharide extract from Porphyromonas gingivalis. Infect Immun 67:2841–2846PubMedPubMedCentralGoogle Scholar
  108. Kara A, Akman S, Ozkanlar S et al (2013) Immune modulatory and antioxidant effects of melatonin in experimental periodontitis in rats. Free Radic Biol Med 55:21–26PubMedCrossRefGoogle Scholar
  109. Kawai T, Matsuyama T, Hosokawa Y et al (2006) B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol 169:987–998PubMedPubMedCentralCrossRefGoogle Scholar
  110. Kikkert R, Laine ML, Aarden LA, van Winkelhoff AJ (2007) Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria. Oral Microbiol Immunol 22:145–151PubMedCrossRefGoogle Scholar
  111. Kikuchi T, Hahn CL, Tanaka S, Barbour SE, Schenkein HA, Tew JG (2004) Dendritic cells stimulated with Actinobacillus actinomycetemcomitans elicit rapid gamma interferon responses by natural killer cells. Infect Immun 72:5089–5096PubMedPubMedCentralCrossRefGoogle Scholar
  112. Kim JH, Lee DE, Cha JH, Bak EJ, Yoo YJ (2014) Receptor activator of nuclear factor-kB ligand and sclerostin expression in osteocytes of alveolar bone in rats with ligature-induced periodontitis. J Periodontol 85:e370–e378PubMedCrossRefGoogle Scholar
  113. Kim JH, Lee DE, Woo GH, Cha JH, Bak EJ, Yoo YJ (2015) Osteocytic sclerostin expression in alveolar bone in rats with diabetes mellitus and ligature-induced periodontitis. J Periodontol 86:1005–1011PubMedCrossRefGoogle Scholar
  114. Kirkwood KL, Li F, Rogers JE et al (2007) A p38alpha selective mitogen-activated protein kinase inhibitor prevents periodontal bone loss. J Pharmacol Exp Ther 320:56–63PubMedCrossRefGoogle Scholar
  115. Klein DC, Raisz LG (1970) Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology 86:1436–1440PubMedCrossRefGoogle Scholar
  116. Kong YY, Yoshida H, Sarosi I et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323PubMedCrossRefGoogle Scholar
  117. Kook YA, Lee SK, Son DH et al (2009) Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells. Cell Biol Int 33:424–428PubMedCrossRefGoogle Scholar
  118. Kotake S, Udagawa N, Takahashi N et al (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103:1345–1352PubMedPubMedCentralCrossRefGoogle Scholar
  119. Koutouzis T, Haber D, Shaddox L, Aukhil I, Wallet SM (2009) Autoreactivity of serum immunoglobulin to periodontal tissue components: a pilot study. J Periodontol 80:625–633PubMedPubMedCentralCrossRefGoogle Scholar
  120. Kulkarni C, Kinane DF (2014) Host response in aggressive periodontitis. Periodontol 2000 65:79–91PubMedCrossRefGoogle Scholar
  121. Kuziel WA, Greene WC (1990) Interleukin-2 and the IL-2 receptor: new insights into structure and function. J Invest Dermatol 94:27S–32SPubMedCrossRefGoogle Scholar
  122. Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMedCrossRefGoogle Scholar
  123. Lacey DC, Simmons PJ, Graves SE, Hamilton JA (2009) Proinflammatory cytokines inhibit osteogenic differentiation from stem cells: implications for bone repair during inflammation. Osteoarthritis Cartilage 17:735–742PubMedCrossRefGoogle Scholar
  124. Lappin DF, Kjeldsen M, Sander L, Kinane DF (2000) Inducible nitric oxide synthase expression in periodontitis. J Periodontal Res 35:369–373PubMedCrossRefGoogle Scholar
  125. Lee HJ, Pi SH, Kim Y et al (2009) Effects of nicotine on antioxidant defense enzymes and RANKL expression in human periodontal ligament cells. J Periodontol 80:1281–1288PubMedCrossRefGoogle Scholar
  126. Leppilahti JM, Hernández-Ríos PA, Gamonal JA et al (2014) Matrix metalloproteinases and myeloperoxidase in gingival crevicular fluid provide site-specific diagnostic value for chronic periodontitis. J Clin Periodontol 41:348–356PubMedCrossRefGoogle Scholar
  127. Lin X, Han X, Kawai T, Taubman MA (2011) Antibody to RANKL Ameliorates T cell-mediated Periodontal Bone Resorption. Infect Immun 79:911–7Google Scholar
  128. Listgarten MA (1994) The structure of dental plaque. Periodontol 2000 5:52–65PubMedCrossRefGoogle Scholar
  129. Liu YC, Lerner UH, Teng YT (2010) Cytokine responses against periodontal infection: protective and destructive roles. Periodontol 2000 52:163–206PubMedCrossRefGoogle Scholar
  130. Loe H, Theilade E, Jensen SB (1965) Experimental gingivitis in man. J Periodontol 36:177–187PubMedCrossRefGoogle Scholar
  131. Lohinai Z, Benedek P, Feher E et al (1998) Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat. Br J Pharmacol 123:353–360PubMedPubMedCentralCrossRefGoogle Scholar
  132. Malcolm J, Awang RA, Oliver-Bell J et al (2015) IL-33 exacerbates periodontal disease through induction of RANKL. J Dent Res 94:968–975PubMedCrossRefGoogle Scholar
  133. Massey HM, Flanagan AM (1999) Human osteoclasts derive from CD14-positive monocytes. Br J Haematol 106:167–170PubMedCrossRefGoogle Scholar
  134. Matejka M, Partyka L, Ulm C, Solar P, Sinzinger H (1998) Nitric oxide synthesis is increased in periodontal disease. J Periodontal Res 33:517–518PubMedCrossRefGoogle Scholar
  135. Mayer Y, Balbir-Gurman A, Machtei EE (2009) Anti-tumor necrosis factor-alpha therapy and periodontal parameters in patients with rheumatoid arthritis. J Periodontol 80:1414–1420PubMedCrossRefGoogle Scholar
  136. Menezes R, Garlet TP, Letra A et al (2008) Differential patterns of receptor activator of nuclear factor kappa B ligand/osteoprotegerin expression in human periapical granulomas: possible association with progressive or stable nature of the lesions. J Endod 34:932–938PubMedPubMedCentralCrossRefGoogle Scholar
  137. Miley DD, Garcia MN, Hildebolt CF et al (2009) Cross-sectional study of vitamin D and calcium supplementation effects on chronic periodontitis. J Periodontol 80:1433–1439PubMedPubMedCentralCrossRefGoogle Scholar
  138. Mize TW, Sundararaj KP, Leite RS, Huang Y (2015) Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis. J Periodontal Res 50:315–319PubMedCrossRefGoogle Scholar
  139. Mogi M, Otogoto J, Ota N, Inagaki H, Minami M, Kojima K (1999) Interleukin 1 beta, interleukin 6, beta 2-microglobulin, and transforming growth factor-alpha in gingival crevicular fluid from human periodontal disease. Arch Oral Biol 44:535–539PubMedCrossRefGoogle Scholar
  140. Mosmann TR, Schumacher JH, Street NF et al (1991) Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev 123:209–229PubMedCrossRefGoogle Scholar
  141. Mostafa NZ, Uludağ H, Varkey M, Dederich DN, Doschak MR, El-Bialy TH (2011) In vitro osteogenic induction of human gingival fibroblasts for bone regeneration. Open Dent J 5:139–145PubMedPubMedCentralCrossRefGoogle Scholar
  142. Moussion C, Ortega N, Girard JP (2008) The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’. PLoS One 3, e3331PubMedPubMedCentralCrossRefGoogle Scholar
  143. Murphy KM, Reiner SL (2002) The lineage decisions of helper T cells. Nat Rev Immunol 2:933–944PubMedCrossRefGoogle Scholar
  144. Naundorf S, Schroder M, Hoflich C, Suman N, Volk HD, Grutz G (2009) IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells. Eur J Immunol 39:1066–1077PubMedCrossRefGoogle Scholar
  145. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A 89:3030–3034PubMedPubMedCentralCrossRefGoogle Scholar
  146. Nile CJ, Barksby E, Jitprasertwong P, Preshaw PM, Taylor JJ (2010) Expression and regulation of interleukin-33 in human monocytes. Immunology 130:172–180PubMedPubMedCentralCrossRefGoogle Scholar
  147. Nowak M, Krämer B, Haupt M et al (2013) Activation of invariant NK T cells in periodontitis lesions. J Immunol 190:2282–2291PubMedPubMedCentralCrossRefGoogle Scholar
  148. Nussbaum G, Shapira L (2011) How has neutrophil research improved our understanding of periodontal pathogenesis. J Clin Periodontol 38(Suppl 11):49–59PubMedCrossRefGoogle Scholar
  149. Offenbacher S, Odle BM, Van Dyke TE (1986) The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. J Periodontal Res 21:101–112PubMedCrossRefGoogle Scholar
  150. Ozçaka O, Nalbantsoy A, Buduneli N (2011) Interleukin-17 and interleukin-18 levels in saliva and plasma of patients with chronic periodontitis. J Periodontal Res 46:592–598PubMedGoogle Scholar
  151. Page RC, Eke PI (2007) Case definitions for use in population-based surveillance of periodontitis. J Periodontol 78:1387–1399PubMedCrossRefGoogle Scholar
  152. Page RC, Kornman KS (1997) The pathogenesis of human periodontitis: an introduction. Periodontol 2000 14:9–11PubMedCrossRefGoogle Scholar
  153. Park AY, Scott P (2001) Il-12: keeping cell-mediated immunity alive. Scand J Immunol 53:529–532PubMedCrossRefGoogle Scholar
  154. Pelletier M, Maggi L, Micheletti A et al (2010) Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 115:335–343PubMedCrossRefGoogle Scholar
  155. Pradeep AR, Roopa Y, Swati PP (2008) Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of periodontal disease. J Periodontal Res 43:712–716PubMedCrossRefGoogle Scholar
  156. Pradeep AR, Priyanka N, Kalra N, Naik SB, Singh SP, Martande S (2012) Clinical efficacy of subgingivally delivered 1.2-mg simvastatin in the treatment of individuals with Class II furcation defects: a randomized controlled clinical trial. J Periodontol 83:1472–1479PubMedCrossRefGoogle Scholar
  157. Pradeep AR, Kumari M, Rao NS, Martande SS, Naik SB (2013) Clinical efficacy of subgingivally delivered 1.2% atorvastatin in chronic periodontitis: a randomized controlled clinical trial. J Periodontol 84:871–879PubMedCrossRefGoogle Scholar
  158. Pradeep AR, Karvekar S, Nagpal K, Patnaik K, Guruprasad CN, Kumaraswamy KM (2015) Efficacy of locally delivered 1.2% rosuvastatin gel to non-surgical treatment of patients with chronic periodontitis: a randomized, placebo-controlled clinical trial. J Periodontol 86:738–745PubMedCrossRefGoogle Scholar
  159. Quinn JM, Elliott J, Gillespie MT, Martin TJ (1998) A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro. Endocrinology 139:4424–4427PubMedCrossRefGoogle Scholar
  160. Rams TE, Listgarten MA, Slots J (2006) Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis subgingival presence, species-specific serum immunoglobulin G antibody levels, and periodontitis disease recurrence. J Periodontal Res 41:228–234PubMedCrossRefGoogle Scholar
  161. Ritz HL (1967) Microbial population shifts in developing human dental plaque. Arch Oral Biol 12:1561–1568PubMedCrossRefGoogle Scholar
  162. Roberts HC, Moseley R, Sloan AJ, Youde SJ, Waddington RJ (2008) Lipopolysaccharide alters decorin and biglycan synthesis in rat alveolar bone osteoblasts: consequences for bone repair during periodontal disease. Eur J Oral Sci 116:207–216PubMedPubMedCentralCrossRefGoogle Scholar
  163. Rodrigues TL, Marchesan JT, Coletta RD et al (2007) Effects of enamel matrix derivative and transforming growth factor-beta1 on human periodontal ligament fibroblasts. J Clin Periodontol 34:514–522PubMedCrossRefGoogle Scholar
  164. Rogers JE, Li F, Coatney DD et al (2007) A p38 mitogen-activated protein kinase inhibitor arrests active alveolar bone loss in a rat periodontitis model. J Periodontol 78:1992–1998PubMedCrossRefGoogle Scholar
  165. Ryder MI (2010) Comparison of neutrophil functions in aggressive and chronic periodontitis. Periodontol 2000 53:124–137PubMedCrossRefGoogle Scholar
  166. Saidenberg-Kermanac’h N, Bessis N, Lemeiter D, de Vernejoul MC, Boissier MC, Cohen-Solal M (2004) Interleukin-4 cellular gene therapy and osteoprotegerin decrease inflammation-associated bone resorption in collagen-induced arthritis. J Clin Immunol 24:370–378PubMedCrossRefGoogle Scholar
  167. Sasaki H, Okamatsu Y, Kawai T, Kent R, Taubman M, Stashenko P (2004) The interleukin-10 knockout mouse is highly susceptible to Porphyromonas gingivalis-induced alveolar bone loss. J Periodontal Res 39:432–441PubMedCrossRefGoogle Scholar
  168. Sato K, Suematsu A, Okamoto K et al (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203:2673–2682PubMedPubMedCentralCrossRefGoogle Scholar
  169. Schröder HE, Lindhe J (1981) Conditions and pathological features of rapidly destructive, experimental periodontitis in dogs. J Periodontol 51:6–19Google Scholar
  170. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349–361PubMedPubMedCentralCrossRefGoogle Scholar
  171. Sgolastra F, Petrucci A, Gatto R, Giannoni M, Monaco A (2011) Long-term efficacy of subantimicrobial-dose doxycycline as an adjunctive treatment to scaling and root planing: a systematic review and meta-analysis. J Periodontol 82:1570–1581PubMedCrossRefGoogle Scholar
  172. Shaddox L, Wiedey J, Bimstein E et al (2010) Hyper-responsive phenotype in localized aggressive periodontitis. J Dent Res 89:143–148PubMedPubMedCentralCrossRefGoogle Scholar
  173. Slots J (2010) Human viruses in periodontitis. Periodontol 2000 53:89–110PubMedCrossRefGoogle Scholar
  174. Stabholz A, Soskolne WA, Shapira L (2010) Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol 2000 53:138–153PubMedCrossRefGoogle Scholar
  175. Steinsvoll S, Halstensen TS, Schenck K (1999) Extensive expression of TGF-beta1 in chronically-inflamed periodontal tissue. J Clin Periodontol 26:366–373PubMedCrossRefGoogle Scholar
  176. Tang H, Mattheos N, Yao Y, Jia Y, Ma L, Gong P (2015) In vivo osteoprotegerin gene therapy preventing bone loss induced by periodontitis. J Periodontal Res 50:434–443PubMedCrossRefGoogle Scholar
  177. Taut AD, Jin Q, Chung JH et al (2013) Sclerostin antibody stimulates bone regeneration after experimental periodontitis. J Bone Miner Res 28:2347–2356PubMedCrossRefGoogle Scholar
  178. Teles RP, Likhari V, Socransky SS, Haffajee AD (2009) Salivary cytokine levels in subjects with chronic periodontitis and in periodontally healthy individuals: a cross-sectional study. J Periodontal Res 44:411–417PubMedPubMedCentralCrossRefGoogle Scholar
  179. Teles R, Teles F, Frias-Lopez J, Paster B, Haffajee A (2013) Lessons learned and unlearned in periodontal microbiology. Periodontol 2000 62:95–162PubMedPubMedCentralCrossRefGoogle Scholar
  180. Teng YT (2006a) Protective and destructive immunity in the periodontium: Part 1--innate and humoral immunity and the periodontium. J Dent Res 85:198–208PubMedCrossRefGoogle Scholar
  181. Teng YT (2006b) Protective and destructive immunity in the periodontium: Part 2--T-cell-mediated immunity in the periodontium. J Dent Res 85:209–219PubMedCrossRefGoogle Scholar
  182. Teng YT, Nguyen H, Gao X et al (2000) Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest 106:R59–R67PubMedPubMedCentralCrossRefGoogle Scholar
  183. Teng YT, Mahamed D, Singh B (2005) Gamma interferon positively modulates Actinobacillus actinomycetemcomitans-specific RANKL+ CD4+ Th-cell-mediated alveolar bone destruction in vivo. Infect Immun 73:3453–3461PubMedPubMedCentralCrossRefGoogle Scholar
  184. Thumbigere-Math V, Michalowicz BS, Hodges JS et al (2014) Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw. J Periodontol 85:226–233CrossRefPubMedGoogle Scholar
  185. Thunell DH, Tymkiw KD, Johnson GK et al (2010) A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodontal Res 45:148–152PubMedCrossRefGoogle Scholar
  186. Tjoa ST, de Vries TJ, Schoenmaker T, Kelder A, Loos BG, Everts V (2008) Formation of osteoclast-like cells from peripheral blood of periodontitis patients occurs without supplementation of macrophage colony-stimulating factor. J Clin Periodontol 35:568–575PubMedCrossRefGoogle Scholar
  187. Tomomatsu N, Aoki K, Alles N et al (2009) LPS-induced inhibition of osteogenesis is TNF-alpha dependent in a murine tooth extraction model. J Bone Miner Res 24:1770–1781PubMedCrossRefGoogle Scholar
  188. Tonetti MS, Mombelli A (1999) Early-onset periodontitis. Ann Periodontol 4:39–53PubMedCrossRefGoogle Scholar
  189. Trombone AP, Ferreira SBJ, Raimundo FM et al (2009) Experimental periodontitis in mice selected for maximal or minimal inflammatory reactions: increased inflammatory immune responsiveness drives increased alveolar bone loss without enhancing the control of periodontal infection. J Periodontal Res 44:443–451PubMedCrossRefGoogle Scholar
  190. Tymkiw KD, Thunell DH, Johnson GK et al (2011) Influence of smoking on gingival crevicular fluid cytokines in severe chronic periodontitis. J Clin Periodontol 38:219–228PubMedCrossRefGoogle Scholar
  191. Ugar-Cankal D, Ozmeric N (2006) A multifaceted molecule, nitric oxide in oral and periodontal diseases. Clin Chim Acta 366:90–100PubMedCrossRefGoogle Scholar
  192. Van Dyke TE, Hasturk H, Kantarci A et al (2015) Proresolving nanomedicines activate bone regeneration in periodontitis. J Dent Res 94:148–156PubMedPubMedCentralCrossRefGoogle Scholar
  193. Verstappen J, Von den Hoff JW (2006) Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease. J Dent Res 85:1074–1084PubMedCrossRefGoogle Scholar
  194. Wang YH, Jiang J, Zhu Q et al (2010) Porphyromonas gingivalis lipids inhibit osteoblastic differentiation and function. Infect Immun 78:3726–3735PubMedPubMedCentralCrossRefGoogle Scholar
  195. Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL (2005) IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 115:282–290PubMedPubMedCentralCrossRefGoogle Scholar
  196. Wolff K (1972) The langerhans cell. Curr Probl Dermatol 4:79–145PubMedCrossRefGoogle Scholar
  197. Yasuda H, Shima N, Nakagawa N et al (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597–3602PubMedPubMedCentralCrossRefGoogle Scholar
  198. Yu JJ, Ruddy MJ, Wong GC et al (2007) An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals. Blood 109:3794–3802PubMedPubMedCentralCrossRefGoogle Scholar
  199. Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA (2013) The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol 84:332–351PubMedCrossRefGoogle Scholar
  200. Zhang X, Teng YT (2006) Interleukin-10 inhibits gram-negative-microbe-specific human receptor activator of NF-kappaB ligand-positive CD4 + −Th1-cell-associated alveolar bone loss in vivo. Infect Immun 74:4927–4931PubMedPubMedCentralCrossRefGoogle Scholar
  201. Zhong Y, Slade GD, Beck JD, Offenbacher S (2007) Gingival crevicular fluid interleukin-1beta, prostaglandin E2 and periodontal status in a community population. J Clin Periodontol 34:285–293PubMedCrossRefGoogle Scholar
  202. Zhong Q, Ding C, Wang M, Sun Y, Xu Y (2012) Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: a meta-analysis based on 14 case–control studies. Cytokine 60:47–54PubMedCrossRefGoogle Scholar
  203. Zwerina J, Hayer S, Tohidast-Akrad M et al (2004) Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum 50:277–290PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Kristina Bertl
    • 1
    • 2
  • Peter Pietschmann
    • 3
  • Andreas Stavropoulos
    • 1
  1. 1.Department of Periodontology, Faculty of OdontologyUniversity of MalmöMalmöSweden
  2. 2.Division of Oral SurgeryUniversity Clinic of Dentistry, Medical University of ViennaViennaAustria
  3. 3.Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and ImmunologyMedical University ViennaViennaAustria

Personalised recommendations