Association of periodontitis with rheumatoid arthritis and atherosclerosis: Novel paradigms in etiopathogeneses and management?

Open Access Rheumatology: Research and Reviews

Volumn 2, Issue , 2010, Pages 1-16

  Soory, Mena ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Atherosclerosis; Cytokines; Periodontal pathogens; Periodontitis; RA; Therapeutic targets

Indexed keywords

ADALIMUMAB; C REACTIVE PROTEIN; CORTICOSTEROID; CYCLIC CITRULLINATED PEPTIDE ANTIBODY; DENOSUMAB; DIPYRIDAMOLE; DISEASE MODIFYING ANTIRHEUMATIC DRUG; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ETANERCEPT; FC RECEPTOR; HEAT SHOCK PROTEIN 70; HLA DR ANTIGEN; INFLIXIMAB; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; INTERLEUKIN 17; INTERLEUKIN 6; INTERLEUKIN 6 ANTIBODY; METHOTREXATE; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PREDNISONE; PROTEIN ARGININE DEIMINASE; SERUM AMYLOID A; SIMVASTATIN; TOCILIZUMAB; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN;

ANTIINFLAMMATORY ACTIVITY; ATHEROGENESIS; ATHEROSCLEROSIS; AUTOIMMUNITY; BRAIN ISCHEMIA; CARDIOVASCULAR RISK; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DEBRIDEMENT; DENTAL CARIES; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG RESPONSE; DRUG TARGETING; GINGIVITIS; GRAM NEGATIVE BACTERIUM; HUMAN; INFLAMMATION; JUVENILE RHEUMATOID ARTHRITIS; LEUKAPHERESIS; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PERIODONTITIS; PREVENTIVE DENTISTRY; PROTEIN EXPRESSION; REVIEW; RHEUMATOID ARTHRITIS; RISK FACTOR;

EID: 77955335689     PISSN: None     EISSN: 1179156X     Source Type: Book Series    
DOI: 10.2147/oarrr.s10928     Document Type: Review

References (143)

1. Banks M, Flint J, Bacon P, Kitas G. Rheumatoid arthritis is an independent risk factor for ischemic heart disease. Arthritis Rheum. 2000; 43 (suppl):385.
2. Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003;107(9):1303-1307.
3. Van Doornum S, McNoll G, Wicks IP. Accelerated atherosclerosis: an extra-articular feature of rheumatoid arthritis. Arthritis Rheum. 2002;46(4):862-873.
4. Lowe GDO, Danesh J. Classical and emerging risk factors for cardiovascular disease. Semin Vasc Med. 2005;2(3):229-445.
5. Abou-Raya A, Abou-Raya S. Inflammation: a pivotal link between autoimmune diseases and atherosclerosis. Autoimmun Rev. 2006;5(5): 331-337.
6. Abou-Raya S, Naim A, Abu-El KH, El BS. Coronary artery disease and periodontal disease: is there a link. Angiology. 2002;53(2): 141-148.
7. Rutger Persson G, Ohlsson O, Pettersson T, Renvert S. Chronic periodontitis, a significant relationship with acute myocardial infarction. Eur Heart J. 2003;24(23):2108-2115.
8. Malthaner SC, Moore S, Mills M. Investigation of the association between angiographically defined coronary artery disease and periodontal disease. J Periodontol. 2002;73(10):1169-1176.
9. Irwin CR, Myrillas TT, Traynor P, Leadbetter N, Cawston TE. The role of soluble interleukin (IL)-6 receptor in mediating the effects of IL-6 on matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression by gingival fibroblasts. J Periodontol. 2002;73(7): 741-747.
10. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809-1820.
11. Taubman MA, Valverde P, Han X, Kawai T. Immune response: the key to bone resorption in periodontal disease. J Periodontol. 2005; 76 Suppl 11:2033S-2041S.
12. Gemmell E, Yamazaki K, Seymour GJ. Destructive periodontitis lesions are determined by the nature of the lymphocytic response. Crit Rev Oral Biol Med. 2002;13(1):17-34.
13. Kinane DF, Demuth DR, Gorr SU, Hajishengallis GN, Martin MH. Human variability in innate immunity. Periodontol 2000. 2007;45(1): 14-34.
14. Firestein GS. Aetiology and pathogenesis of rheumatoid arthritis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB eds. Textbook of Rheumatology. 6th ed. Philadelphia, PA: Saunders;2001: 921-966.
15. Darveau RP, Tanner A, Page RC. The microbial challenge in periodontitis. Periodontol. 2000.1997;14(1):12-32.
16. Brown LJ, Loe H. Prevalence, extent, severity and progression of periodontal disease. Periodontol. 2000;1993;2(1):57-71.
17. Libby P, Ridker P, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-1143.
18. Mercado FB, Marshall RI, Klestov AC, Bartold PM. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001;72(6):779-787.
19. Abou-Raya A, Abou-Raya S. Periodontal disease and rheumatoid arthritis: is there a link. Scand J Rheum. 2005;34(5):408-410.
20. Soory M. Periodontal diseases and rheumatoid arthritis: A coincident model for therapeutic intervention. Curr Drug Metab. 2007;8(8): 750-757.
21. Abou-Raya S, Abou-Raya A, Naim A, Abuelkheir H. Rheumatoid arthritis, periodontal disease and coronary artery disease. Clin Rheumatol. 2008;27(4):421-427.
22. Page RC, Eke PI. Case definitions for use in population-based surveillance of periodontitis. J Periodontol. 2007;78(7):1387-1399.
23. Hamdulay SS, Mason JC. Disease-modifying anti-rheumatic drugs -do they reduce cardiac complications of RA? Heart. 2009;95(18): 1502-1507.
24. Wu B, Fukuo K, Suzuki K, Yoshino G, Kazumi T. Relationships of systemic oxidative stress to body fat distribution, adipokines and inflammatory markers in healthy middle aged women. Endocr J. 2009;56(6):773-782.
25. Madan JC, Davis JM, Craig WY, et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine. 2009;47(1):61-64.
26. Derosa G, Ferrari I, D'Angelo A, et al. Oral fat load effects on inflammation and endothelial stress markers in healthy subjects. Heart Vessels. 2009;24(3):204-210.
27. Rahman ZA, Soory M. Antioxidant effects of glutathione and IGF in a hyperglycaemic cell culture model of fibroblasts: some actions of advanced glycaemic end products (AGE) and nicotine. Endocr Metab Immune Disord Drug Targets. 2006;6(3):279-286.
28. Figuero-Ruiz E, Soory M, Cerero R, Bascones A. Oxidant/antioxidant interactions of nicotine, Coenzyme Q10, Pycnogenol and phytoestrogens in oral periosteal fibroblasts and MG63 osteoblasts, Steroids. 2006;71(13-14):1062-1072.
29. Soory M. A role for non-antimicrobial actions of tetracyclines in combating oxidative stress in periodontal and metabolic diseases. Open Dent J. 2008;2:5-12.
30. Soory M. Redox status in periodontal and systemic inflammatory conditions including associated neoplasias: Antioxidants as adjunctive therapy? Infect Disord Drug Targets. 2009;9(Suppl):415-427.
31. Sorensen LK, Havemose-Poulsen A, Bendtzen K, Holmstrup P. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors. J Periodontol. 2009;80(2):282-289.
32. Schett G, Redlich K, Xu Q, et al. Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiinflammatory drugs. J Clin Invest.1998;102(2):302-311.
33. Bain J, Lester SR, Henry WD, et al. Comparative gender differences in local and systemic concentrations of pro-inflammatory cytokines in rats with experimental periodontitis, J Periodont Res. 2009; 44(1):133-140.
34. Soory M. Biomarkers of diabetes mellitus and rheumatoid arthritis associated with oxidative stress, applicable to periodontal diseases. Curr Topics Ster Res. 2004;4:1-17.
35. Liao F, Li Z, Wang Y, Shi B, Gong Z, Cheng X. Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated rheumatoid arthritis. Med Hypothesis. 2009;72(6):732-735.
36. Behl Y, Siqueira M, Ortiz J, et al. Activation of the acquired immune response reduces coupled bone formation in response to a periodontal pathogen. J Immunol. 2008;181(12);8711-8718.
37. Mikuls TR, Payne JB, Reinhardt RA, et al. Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol. 2009;9(1):38-42.
38. Al-Katma MK, Bissada NF, Bordeaux JM, Sue J, Askari AD. Control of periodontal infection reduces the severity of active rheumatoid arthritis. J Clin Rheumatol. 2007;13(3):134-137.
39. Ogrendik M. Periodontopathic bacteria and rheumatoid arthritis: is there a link? J Clin Rheumatol. 2008;14(5):310-311.
40. Moen K, Brun JG, Valen M, et al. Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol. 2006;24(6):656-663.
41. McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas Gingivalis, peptidylarginine deiminase. Infect Immun. 1999;67(7):3248-3256.
42. Pischon N, Roehner E, Hocke A, et al. Effects of porphyromonas gingivalis on cell cycle progression and apoptosis of primary human chondrocytes. Ann Rheum Dis. 2009;68(12):1902-1907.
43. Cuesta IA, Sud S, Song Z, et al. T-cell receptor (Vbeta) bias in the response of rheumatoid arthritis synovial fluid T cells to connective tissue antigens. Scand J Rheumatol. 1997;26(3):166-173.
44. Leung KP, Torres BA. Prevotella intermedia stimulates expansion of Vbeta-specific CD4(+) T cells. Infect Immun. 2000;68(9):5420-5424.
45. Gibson FC 3rd, Genco CA. Porphyromonas Gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs. Curr Pharm Des. 2007; 13(36):3665-3675.
46. Galkina E, Ley K. Immune and Inflammatory Mechanisms of Atherosclerosis. Annu Rev Immunol. 2009;27:165-197.
47. Soory M. Relevance of dyslipidemia and its consequences in periodontal patients with co-existing cardiovascular disease and diabetes mellitus: Therapeutic targets. Recent Patents on Endocrine, Metabolic and Immune Drug Discovery. 2009;3(3):214-224.
48. Rizzo M, Spinas GA, Cesur M, Ozbalkan Z, Rini GB, Berneis K. Atherogenic lipoprotein phenotype and LDL size and sub classes in drug-naive patients with early rheumatoid arthritis. Atherosclerosis. 2009;207(2):502-506.
49. Nilsson M, Kopp S. Gingivitis and periodontitis are related to repeated high levels of circulating tumour necrosis factor-alpha in patients with rheumatoid arthritis. J Periodontol. 2008;79(9):1689-1696.
50. Pischon N, Pischon T, Kroger J, et al. Association among rheumatoid arthritis, oral hygiene and periodontitis. J Periodontol. 2008; 79(6):979-986.
51. Smolik I, Robinson D, El-Gabalawy HS. Periodontitis and rheumatoid arthritis: epidemiologic, clinical and immunologic associations. Compend Contin Educ Dent. 2009;30(4):188-190.
52. Soory M. Relevance of nutritional antioxidants in metabolic syndrome, ageing and cancer: Potential for therapeutic targeting. Infect Disord Drug Targets. 2009;9(4):400-414.
53. de Pablo P, Chapple IL, Buckley CD, Dietrich T. Periodontitis in systemic rheumatic diseases. Nat Rev Rheumatol. 2009;5(4):218-224.
54. Modi DK, Chopra VS, Bhau U. Rheumatoid arthritis and periodontitis: biological links and the emergence of dual purpose therapies. Indian J Dent Res. 2009;20(1):86-90.
55. Stamatelopoulos KS, Kitas GD, Papamichael CM, et al. Oral health and orthodontic considerations in children with idiopathic arthritis: review of the literature and report of a case. J Ir Dent Assoc. 2008; 54(1):29-36.
56. Leksell E, Ernberg M, Magnusson B, Hedenberg-Magnusson B. Intraoral condition in children with juvenile idiopathic arthritis compared to controls. Int J Paediatr Dent. 2008;18(6):423-433.
57. Reichert S, Stein J, Fuchs C, John V, Schaller HG, Machulla HK. Are there common human leucocyte antigen associations in juvenile idiopathic arthritis and periodontitis? J Clin Periodontol. 2007;34(6): 492-498.
58. Abou-Raya S, Abou-Raya A, Naim A, Abuelkheir H. Chronic inflammatory autoimmune disorders and atherosclerosis. Ann NY Acad Sci. 2007;1107:56-67.
59. Stamatelopoulos KS, Kitas GD, Papamichael CM, et al. Atherosclerosis in Rheumatoid Arthritis Versus Diabetes. A Comparative Study. Arterioscler Thromb Vasc Biol. 2009;29(1):1-7.
60. Targońska-Stepniak B, Dryglewska M, Majdan M. Adiponectin and lipid serum concentrations in patients with rheumatoid arthritis. Rheumatol Int. 2009:30(6):731-737.
61. Wang L, Zheng J, Bai X, et al. ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries. Circ Res. 2009;104(5):688-698.
62. Wang S, Yiu KH, Mok MY, et al. Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis. J Intern Med. 2009;266(5):445-452.
63. Tanasescu C, Jurcut C, Jurcut R, Ginghina C. Vascular disease in rheumatoid arthritis: from subclinical lesions to cardiovascular risk. Eur J Intern Med. 2009;20(4):348-354.
64. Yao Z, Yang J, Pan L, Chen Z. Periodontal treatment: potential to reduce cardiovascular morbidity and/mortality. Med Hypotheses. 2009;73(1):33-35.
65. Eley BM, Soory M, Manson D. The effect of systemic factors on the periodontal tissues. In: Periodontics. 6th ed. Amsterdam. The Netherlands: Elsevier; 2010:107-125.
66. Monteiro AM, Jardini MA, Alves S, et al. Cardiovascular disease parameters in periodontitis. J Periodontol. 2009;80(3):378-388.
67. Fentoǧlu O, Oz G, Taşdelen P, Uskun E, Aykac Y, Bozkurt FY. Periodontal status in subjects with hyperlipidemia. J Periodontol. 2009; 80(2):267-273.
68. Banihashemrad SA, Moeintaghavi A, Rafighdoost A. Relationship between cholesterol and triglyceride blood values and periodontal parameters in patients of Mashhad health centre. NY State Dent J. 2008;74(5):65-66.
69. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-442.
70. Scott DL, Kingsley GH. Tumor necrosis factor inhibitors for rheumatoid arthritis. N Engl J Med. 2006;355(7):704-712.
71. Keystone EC. Strategies to control disease in rheumatoid arthritis with tumor necrosis factor antagonists-an opportunity to improve outcomes. Nat Clin Pract Rheumatol. 2006;2(11):594-601.
72. Seriolo B, Paolino S, Sulli A, Ferretti V, Cutolo M. Bone metabolism changes during anti-TNFalpha therapy in patients with active rheumatoid arthritis. Ann N Y Acad Sci. 2006;1069:420-427.
73. Sakai Y, Sakai S, Otsuka T, et al. Efficacy of high-throughput leukocytapheresis for rheumatoid arthriris with a reduced response to infliximab. Ther Apher Dial. 2009;13(3):179-185.
74. Pers JO, Sarau A, Pierre R, Youinou P. Anti-TNF-〈 immunotherapy is associated with increased gingival inflammation without clinical attachment loss in subjects with rheumatoid arthritis. J Periodontol. 2008;79(9):1645-1651.
75. Mayer Y, Balbir-Gurman A, Machtei E. Anti-tumour necrosis factor -alpha therapy and periodontal parameters in patients with rheumatoid arthritis. J Periodontol. 2009;80(9):1414-1420.
76. Oritz P, Bissada NF, Palomo L, et al. Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumour necrosis factor inhibitors. J Periodontol. 2009;80(4):535-540.
77. Renvert S, Lindahl C, Roos-Jansaker AM, Lessem J. Short-term effects of an anti-inflammatory treatment on clinical parameters and serum levels of C-reactive protein and pro-inflammatory cytokines in subjects with periodontitis. J Periodontol. 2009;80(6):892-900.
78. Keersmaekers T, Claes K, Kuypers DR, de Vlam K P, Verschueren P, Westhovens R. Long-term efficacy of infliximab treatment for AAamyloidosis secondary to chronic inflammatory arthritis. Ann Rheum Dis. 2009;68(5):759-761.
79. Papagoras C, Voulgari PC, Drosos AA. Long-term use of adalimumab in the treatment of rheumatic diseases. Open Access Rheumatol Res Rev. 2009;1:51-68.
80. Leibbrandt A, Penninger JM. RANK/RANKL: Regulators of immune responses and bone physiology. Ann NY Acad Sci. 2008;1143:123-150.
81. Horwood N. Lymphocyte-derived cytokines in inflammatory arthritis. Autoimmunity. 2008;41(3):230-238.
82. Teitelbaum SL. Osteoclasts: what do they do and how do they do it? Am J Pathol. 2007;170(2):427-435.
83. Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008;79(8):1569-1576.
84. Schett G. Cells of the synovium in rheumatoid arthritis. Osteoclasts. Arthritis Res Ther. 2007;9(1):203-208.
85. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337-342.
86. Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol. 2007;19(4):376-382.
87. Takahashi N, Udagawa N, Kobayashi Y, Suda T. Generation of osteoclasts in vitro, and assay of osteoclast activity. Methods Mol Med. 2007;135:285-301.
88. Gravallese EM, Manning C, Tsay A, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum. 2000;43(2):250-258.
89. Shigeyama Y, Pap T, Kunzler P, Simmen BR, Gay RE, Gay S. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthritis Rheum. 2000;43(11):2523-2530.
90. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J. Clin Invest. 2000;106(12):1481-1488.
91. Wei S, Kitaura H, Zhou P, Ross FP, Teitelbaum SL. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest. 2005;115(2):282-290.
92. Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 2006;54(1):158-168.
93. Morony S, Warmington K, Adamu S, et al. The inhibition of RANKL causes greater suppression of bone resorption and hypercalcemia compared with bisphosphonates in two models of humoral hypercalcemia of malignancy. Endocrinol. 2005;146(8):3235-3243.
94. Schneeweis LA, Willard D, Milla ME. Functional dissection of osteoprotegerin and its interaction with receptor activator of NF-kappaB ligand. J Biol Chem. 2005;280(50):41155-41164.
95. Schett G, Middleton S, Bolon B, et al. Additive bone-protective effects of anabolic treatment when used in conjunction with RANKL and tumor necrosis factor inhibition in two rat arthritis models. Arthritis Rheum. 2005;52(5):1604-1611.
96. Redlich K, Hayer S, Maie A, et al. Tumor necrosis factor alphamediated joint destruction is inhibited by targeting osteoclasts with osteoprotegerin. Arthritis Rheum. 2002;46(3):85-792.
97. Redlich K, Gortz B, Hayer S, et al. Repair of local bone erosions and reversal of systemic bone loss upon therapy with anti-tumor necrosis factor in combination with osteoprotegerin or parathyroid hormone in tumor necrosis factor-mediated arthritis. Am J Pathol. 2004;164(2): 543-555.
98. Romas E, Sims NA, Hards D, et al. Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. Am J Pathol. 2002;161(4):1419-1427.
99. Jin Q, Cirelli JA, Park CH, et al. RANKL Inhibition through osteoprotegerin blocks bone loss in experimental periodontitis. J Periodontol. 2007;78(7):1300-1308.
100. Schwartz Z, Olivares-Navarrete R, Wieland M, Cochran DL, Boyan BD. Mechanisms regulating increased production of osteoprotegerin by osteoblasts cultured on microstructured titanium surfaces. Biomaterials. 2009;30(20):3390-3396.
101. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19(7):1059-1066.
102. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821-831.
103. Cohen SB, Valen PA, Richlin C. RANKL inhibition with denosumab reduces progression of bone erosions in patients with rheumatoid arthritis: month 6 MRI results. Arthritis Rheum. 2006;54:S831-S836.
104. Yu JJ, Ruddy MJ, Wong GC, et al. 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. 2007;109(9):3794-3802.
105. Yu JJ, Ruddy MJ, Conti HR, Boonanantanasarn K, Gaffen SL. The interleukin-17 receptor plays a gender-dependent role in host protection against Porphyromonas gingivalis-induced periodontal bone loss. Infect Immun. 2008;76(9):4206-4213.
106. Herman S, Kronke G, Schett G. Molecular mechanisms of inflammatory bone damage: emerging targets for therapy. Trends Mol Med. 2008;14(6):245-253.
107. Gabay C, McInnes B. The biological and clinical importance of the new generation cytokines in rheumatic diseases. Arthritis Res Ther. 2009;11(3):230-243.
108. von der Thusen JH, Kuiper J, van Berkel TJ, Biessen EA. Interleukins in atherosclerosis: Molecular pathways and therapeutic potential. Pharmacol Rev. 2003;55(1):133-166.
109. Kramer JM, Gaffen SL. Interleukin-17: a new paradigm in inflammation, autoimmunity and therapy. J Periodontol. 2007;78(6):1083-1093.
110. Takahashi K, Azuma T, Motohira H, Kinane DF, Kitetsu S. The potential role of interleukin-17 in the immunopathology of periodontal disease. J Clin Periodontol. 2005;32(4):369-374.
111. Vernal R, Dutzan N, Chaparro A, Puente J, Valenzuela MA, Gamonal J. Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. J Clin Periodontol. 2005;32(4):383-389.
112. Kotake S, Udagawa N, Takahashi N, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103(9):1345-1352.
113. Zhang Z, Zheng M, Bindas J, Schwarzenberger P, Kolls JK. Critical role of IL-17 receptor signaling in acute TNBS induced colitis. Inflamm Bowel Dis. 2006;12(5):382-388.
114. Lubberts E, van den Bersselaar L, Oppers-Walgreen B, et al. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappaB ligand/osteoprotegerin balance. J Immunol. 2003;70(5):2655-2662.
115. Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H. Protein expression and functional difference of membrane bound and soluble receptor activator of NF-kappaB ligand: Modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun. 2000;275(3):768-775.
116. Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54(9):2817-2829.
117. Malemud CJ. Recent advances in neutralizing the IL-6 pathway in arthritis. Open Access Rheumatol Res Rev. 2009;1:133-150.
118. Visvanathan S, van der Heijde D, Deodhar A, et al. Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis. 2009;68(2):175-182.
119. Axmann R, Bohm C, Kronke G, Zwerina J, Smolen J, Schett G. Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum. 2009;60(9):2747-2756.
120. Lin AE, Liu C-J. The emerging roles of ADAMS-7 and ADAMS-12 matrix metalloproteinases. Open Access Rheumatol Res Rev. 2009;1:121-131.
121. Paulissen G, Rocks N, Gueders MM, et al. Role of ADAM and ADAMTS metalloproteinases in airway diseases. Resp Res. 2009;10(1):127-138.
122. Sabatine MS, Ploughman L, Simonsen KL, et al. Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy. Arterioscler Thromb Vasc Biol. 2008;28(3):562-567.
123. Wagsater D, Bjork H, Zhu C, et al. ADAMTS-4 and -8 are inflammatory regulated enzymes expressed in macrophage-rich areas of human atherosclerotic plaques. Atherosclerosis. 2008;196(2):514-522.
124. Moriguchi-Goto S, Yamashita A, Tamura N, et al. ADAMTS-13 attenuates thrombus formation on type I collagen surface and disrupted plaques under flow conditions. Atherosclerosis. 2009;203(2):409-416.
125. Liu CJ. The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. Nat Clin Pract Rheumatol. 2009;5(1):38-45.
126. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11(1):529-543.
127. Murphy G, Nagase H. Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin. Pract Rheumatol. 2008;4(2):128-135.
128. Rowan AD, Litherland GJ, Hui W, Milner JM. Metalloproteases as potential therapeutic targets in arthritis treatment. Expert Opin Ther Targets. 2008;12(1):1-18.
129. Voros G, Maquoi E, Collen D, Lijnen HR. Differential expression of plasminogen activator inhibitor-1, tumor necrosis factor-alpha, TNFalpha converting enzyme and ADAMTS family members in murine fat territories. Biochim Biophys Acta. 2003;1625(1):36-42.
130. Yun HJ, Yoo WH, Han MK, Lee YR, Kim JS, Lee SI. Epigallocatechin -3-gallate suppresses TNF-alpha-induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts. Rheumatol Int. 2008;29(1):23-29.
131. Luan Y, Kong L, Howell DR, et al. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthr Cartil. 2008;6(11): 1413-1420.
132. Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol. 2000;190(3):300-309.
133. Rudijanto A. The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indone. 2007;39(2):86-93.
134. Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006;85(6):520-523.
135. Pandian A, Arora A, Sperling LS, Khan BV. Targeting multiple dyslipidemias with fixed combinations -focus on extended release niacin and simvastatin. Vasc Health Risk Manag. 2008;4(5):1001-1009.
136. Sundararaj KP, Samuvel DJ, Li Y, et al. Simvastatin suppresses LPSinduced MMP-1 expression in U 937 mononuclear cells by inhibiting protein isoprenylation-mediated ERK activation. J Leukocyte Biol. 2008;84(4):1120-1129.
137. Vaziri H, Naberhojjati-Roodsari R, Tahsili-Fahdan N, et al. Effect of simvastatin administration on periodontitis-associated bone loss in ovariectomised rats. J Periodontol. 2007;78(8):1561-1567.
138. Morris MS, Lee Y, Lavin MT, et al. Injectable simvastatin in periodontal defects and alveolar ridges: pilot studies. J Periodontol. 2008;79(8): 1465-1473.
139. Seto H, Ohba H, Tokunaga K, Hama H, Horibe M, Nagata T. Topical administration of simvastatin recovers alveolar bone loss in rats. J Periodont Res. 2008;43(3):261-267.
140. Lindy O, Suomalainen K, Makela M, Lindy S. Statin use is associated with fewer periodontal lesions: A retrospective study. BMC Oral Health. 2008;8:16-22.
141. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109(23 Suppl 1):39-43.
142. Liao JK, Laufs U. Pleiotropic effects of statins. Ann Rev Pharmacol Toxicol. 2005;45:89-118.
143. Ott C, Schmieder RE. The role of statins in the treatment of the metabolic syndrome. Curr Hypertens Rep. 2009;11(2):143-149.