Animal models to study host-bacteria interactions involved in periodontitis.

Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of are pair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them.

[1]  A. Kuijpers-Jagtman,et al.  Inflammatory responses in two commonly used rat models for experimental tooth movement: comparison with ligature-induced periodontitis. , 2011, Archives of oral biology.

[2]  D. Graves,et al.  Inflammation and Uncoupling as Mechanisms of Periodontal Bone Loss , 2011, Journal of dental research.

[3]  H. Baker,et al.  Tannerella forsythia infection-induced calvarial bone and soft tissue transcriptional profiles. , 2010, Molecular oral microbiology.

[4]  R. Lamont,et al.  Role of Porphyromonas gingivalis Phosphoserine Phosphatase Enzyme SerB in Inflammation, Immune Response, and Induction of Alveolar Bone Resorption in Rats , 2010, Infection and Immunity.

[5]  Y. Li,et al.  Adaptive immune response in osteoclastic bone resorption induced by orally administered Aggregatibacter actinomycetemcomitans in a rat model of periodontal disease. , 2010, Molecular oral microbiology.

[6]  H. Baker,et al.  Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profiles. , 2010, Molecular oral microbiology.

[7]  L. Santambrogio,et al.  Dendritic Cell-Mediated In Vivo Bone Resorption , 2010, The Journal of Immunology.

[8]  S. Ozono,et al.  Blockade of sympathetic b-receptors inhibits Porphyromonas gingivalis-induced alveolar bone loss in an experimental rat periodontitis model. , 2010, Archives of oral biology.

[9]  A. Schmidt,et al.  A murine model of accelerated periodontal disease in diabetes. , 2010, Journal of periodontal research.

[10]  T. Tomofuji,et al.  Experimental periodontitis induces gene expression of proinflammatory cytokines in liver and white adipose tissues in obesity. , 2010, Journal of periodontology.

[11]  T. Tomofuji,et al.  Effects of periodontitis on aortic insulin resistance in an obese rat model , 2010, Laboratory Investigation.

[12]  H. Baker,et al.  Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles. , 2010, Molecular oral microbiology.

[13]  A. Yoshimura,et al.  Green tea catechin inhibits lipopolysaccharide-induced bone resorption in vivo. , 2010, Journal of periodontal research.

[14]  T. Tomofuji,et al.  Preventive effects of a cocoa-enriched diet on gingival oxidative stress in experimental periodontitis. , 2009, Journal of periodontology.

[15]  F. Li,et al.  MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss , 2009, Journal of dental research.

[16]  R. Ernst,et al.  The structurally similar, penta-acylated lipopolysaccharides of Porphyromonas gingivalis and Bacteroides elicit strikingly different innate immune responses. , 2009, Microbial pathogenesis.

[17]  L. C. Spolidorio,et al.  Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis. , 2009, Life sciences.

[18]  R. Chole,et al.  Radiographic and Micro—Computed Tomographic Imaging of Lipopolysaccharide-Mediated Bone Resorption , 2009, The Annals of otology, rhinology, and laryngology.

[19]  Y. Carvalho,et al.  Homeopathic treatment for bone regeneration: experimental study , 2009, Homeopathy.

[20]  I. Tohnai,et al.  Combination with allogenic bone reduces early absorption of beta-tricalcium phosphate (beta-TCP) and enhances the role as a bone regeneration scaffold. Experimental animal study in rat mandibular bone defects. , 2009, Dental materials journal.

[21]  D. Graves,et al.  Activation of the Acquired Immune Response Reduces Coupled Bone Formation in Response to a Periodontal Pathogen1 , 2008, The Journal of Immunology.

[22]  Elden Rowland,et al.  Immune Response and Alveolar Bone Resorption in a Mouse Model of Treponema denticola Infection , 2008, Infection and Immunity.

[23]  Y. Fukusaki,et al.  Lack of Toll-like receptor 4 decreases lipopolysaccharide-induced bone resorption in C3H/HeJ mice in vivo. , 2008, Oral microbiology and immunology.

[24]  Johan R de Jong,et al.  A comparison of micro-CT, microradiography and histomorphometry in bone research. , 2008, Archives of oral biology.

[25]  B. Stegenga,et al.  Vivosorb, Bio-Gide, and Gore-Tex as barrier membranes in rat mandibular defects: an evaluation by microradiography and micro-CT. , 2008, Clinical oral implants research.

[26]  T. Uematsu,et al.  Inorganic Polyphosphate: a Possible Stimulant of Bone Formation , 2007, Journal of dental research.

[27]  A. V. van Winkelhoff,et al.  Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria. , 2007, Oral microbiology and immunology.

[28]  S. Gaffen,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. , 2007, Blood.

[29]  Y. Carvalho,et al.  Effect of calcitonin on bone regeneration in male rats: a histomorphometric analysis. , 2007, International journal of oral and maxillofacial surgery.

[30]  R. Müller,et al.  Fluoxetine treatment increases trabecular bone formation in mice , 2007, Journal of cellular biochemistry.

[31]  W. Giannobile,et al.  Actinobacillus actinomycetemcomitans lipopolysaccharide-mediated experimental bone loss model for aggressive periodontitis. , 2007, Journal of periodontology.

[32]  S. Sathishkumar,et al.  Rat Model of Polymicrobial Infection, Immunity, and Alveolar Bone Resorption in Periodontal Disease , 2007, Infection and Immunity.

[33]  L. Shapira,et al.  Cutting Edge: TLR2 Is Required for the Innate Response to Porphyromonas gingivalis: Activation Leads to Bacterial Persistence and TLR2 Deficiency Attenuates Induced Alveolar Bone Resorption1 , 2006, The Journal of Immunology.

[34]  D. Graves,et al.  Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation , 2006, Journal of dental research.

[35]  D. Graves,et al.  Immunization Enhances Inflammation and Tissue Destruction in Response to Porphyromonas gingivalis , 2006, Infection and Immunity.

[36]  D. Graves,et al.  Diabetes enhances mRNA levels of proapoptotic genes and caspase activity, which contribute to impaired healing. , 2006, Diabetes.

[37]  G. Garlet,et al.  Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors. , 2006, Oral microbiology and immunology.

[38]  J. Polak,et al.  Gene Therapy Progress and Prospects: In tissue engineering , 2005, Gene Therapy.

[39]  P. Veith,et al.  An Immune Response Directed to Proteinase and Adhesin Functional Epitopes Protects against Porphyromonas gingivalis-Induced Periodontal Bone Loss1 , 2005, The Journal of Immunology.

[40]  Ashu Sharma,et al.  Tannerella forsythia-induced Alveolar Bone Loss in Mice Involves Leucine-rich-repeat BspA Protein , 2005, Journal of dental research.

[41]  G. Garlet,et al.  Actinobacillus actinomycetemcomitans-induced periodontal disease in mice: patterns of cytokine, chemokine, and chemokine receptor expression and leukocyte migration. , 2005, Microbes and infection.

[42]  D. Fine,et al.  The Actinobacillus actinomycetemcomitans Autotransporter Adhesin Aae Exhibits Specificity for Buccal Epithelial Cells from Humans and Old World Primates , 2005, Infection and Immunity.

[43]  D. Graves,et al.  Porphyromonas gingivalis fimbriae are pro-inflammatory but do not play a prominent role in the innate immune response to P. gingivalis , 2005 .

[44]  S. Way,et al.  Porphyromonas gingivalis Lipopolysaccharide Contains Multiple Lipid A Species That Functionally Interact with Both Toll-Like Receptors 2 and 4 , 2004, Infection and Immunity.

[45]  A. Dumitrescu,et al.  A model of periodontitis in the rat: effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation. , 2004, Journal of clinical periodontology.

[46]  F. Nociti,et al.  Matrix metalloproteinase-2 may be involved with increased bone loss associated with experimental periodontitis and smoking: a study in rats. , 2004, Journal of periodontology.

[47]  F. C. Gibson,et al.  Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice , 2004, Circulation.

[48]  D. Graves,et al.  Diabetes alters the response to bacteria by enhancing fibroblast apoptosis. , 2004, Endocrinology.

[49]  B. Stegenga,et al.  Therapeutic ultrasound to stimulate osteoconduction; A placebo controlled single blind study using e-PTFE membranes in rats. , 2004, Archives of oral biology.

[50]  C. Schwahn,et al.  Observations on experimental marginal periodontitis in rats. , 2004, Journal of periodontal research.

[51]  G. Seymour,et al.  Differences in mouse strain influence leukocyte and immunoglobulin phenotype response to Porphyromonas gingivalis. , 2003, Oral microbiology and immunology.

[52]  A. Rabie,et al.  Quantitative assessment of early healing of intramembranous and endochondral autogenous bone grafts using micro-computed tomography and Q-win image analyzer. , 2003, International journal of oral and maxillofacial surgery.

[53]  P. Papapanou,et al.  Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E–Null Mice , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[54]  E. Sallum,et al.  Stress may enhance nicotine effects on periodontal tissues. An in vivo study in rats. , 2003, Journal of periodontal research.

[55]  H. Deppe,et al.  Effects of osteopromotive and anti-infective membranes on bone regeneration: an experimental study in rat mandibular defects. , 2003, The International journal of oral & maxillofacial implants.

[56]  J. Osredkar,et al.  Influence of subcutaneous administration of recombinant TNF-alpha on ligature-induced periodontitis in rats. , 2003, Journal of periodontal research.

[57]  D. Graves,et al.  Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. , 2002, The Journal of infectious diseases.

[58]  Fu-min Zhang,et al.  Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT(1) receptors. , 2002, American journal of physiology. Heart and circulatory physiology.

[59]  D. Graves,et al.  Contribution of Interleukin-11 and Prostaglandin(s) in Lipopolysaccharide-Induced Bone Resorption In Vivo , 2002, Infection and Immunity.

[60]  M. Bezerra,et al.  Low-dose doxycycline prevents inflammatory bone resorption in rats. , 2002, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[61]  F. C. Gibson,et al.  Prevention of Porphyromonas gingivalis-Induced Oral Bone Loss following Immunization with Gingipain R1 , 2001, Infection and Immunity.

[62]  S. Barros,et al.  Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study. , 2001, Journal of periodontal research.

[63]  D. Fine,et al.  Colonization and persistence of rough and smooth colony variants of Actinobacillus actinomycetemcomitans in the mouths of rats. , 2001, Archives of oral biology.

[64]  R. Pabst,et al.  Hypothalamic-pituitary-adrenal axis activation by experimental periodontal disease in rats. , 2001, Journal of periodontal research.

[65]  D. Graves,et al.  Tumor Necrosis Factor Modulates Fibroblast Apoptosis, PMN Recruitment, and Osteoclast Formation in Response to P. gingivalis Infection , 2001, Journal of dental research.

[66]  R. DeSalle,et al.  Genes for tight adherence of Actinobacillus actinomycetemcomitans: from plaque to plague to pond scum. , 2001, Trends in microbiology.

[67]  T. Ukai,et al.  Bone resorption and local interleukin-1alpha and interleukin-1beta synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis lipopolysaccharide. , 2001, Journal of periodontal research.

[68]  D. Roopenian,et al.  Genetic Control of Susceptibility toPorphyromonas gingivalis-Induced Alveolar Bone Loss in Mice , 2000, Infection and Immunity.

[69]  J. Penninger,et al.  Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. , 2000, The Journal of clinical investigation.

[70]  M. Bezerra,et al.  Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats. , 2000, Journal of periodontology.

[71]  D. Roopenian,et al.  Heterogeneity of Porphyromonas gingivalis strains in the induction of alveolar bone loss in mice. , 2000, Oral microbiology and immunology.

[72]  D. Graves,et al.  Interleukin-1 and Tumor Necrosis Factor Activities Partially Account for Calvarial Bone Resorption Induced by Local Injection of Lipopolysaccharide , 1999, Infection and Immunity.

[73]  D. Roopenian,et al.  CD4+ T Cells and the Proinflammatory Cytokines Gamma Interferon and Interleukin-6 Contribute to Alveolar Bone Loss in Mice , 1999, Infection and Immunity.

[74]  L. Kesavalu,et al.  Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin , 1998, Infection and Immunity.

[75]  A. Salzman,et al.  Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature‐induced periodontitis in the rat , 1998, British journal of pharmacology.

[76]  D. Graves,et al.  IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. , 1998, Journal of immunology.

[77]  T. Suzuki,et al.  In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats. , 1995, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[78]  E. Hedner,et al.  Efficacy of bone morphogenetic protein (BMP) with osteopromotive membranes--an experimental study in rat mandibular defects. , 1995, European journal of oral sciences.

[79]  D. Roopenian,et al.  Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice. , 1994, Archives of oral biology.

[80]  L. Rosivall,et al.  Neurogenic component in ligature-induced periodontitis in the rat. , 1994, Journal of clinical periodontology.

[81]  C. Dahlin,et al.  Bone regeneration by the osteopromotion technique using bioabsorbable membranes: an experimental study in rats. , 1993, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[82]  D. Case,et al.  Cell populations associated with active probing attachment loss. , 1992, Journal of periodontology.

[83]  R. Genco,et al.  Periodontal bone level and gingival proteinase activity in gnotobiotic rats immunized with Bacteroides gingivalis. , 1991, Oral microbiology and immunology.

[84]  H. Okada,et al.  Effect of infection with Eikenella corrodens on the progression of ligature-induced periodontitis in rats. , 1990, Journal of periodontal research.

[85]  G. Mundy,et al.  Effects of interleukin-1 on bone turnover in normal mice. , 1989, Endocrinology.

[86]  R. Genco,et al.  Infection with a gram-negative organism stimulates gingival collagenase production in non-diabetic and diabetic germfree rats. , 1988, Journal of periodontal research.

[87]  S. Nyman,et al.  Healing of Bone Defects by Guided Tissue Regeneration , 1988, Plastic and reconstructive surgery.

[88]  M. Levine,et al.  Effect of anaerobiosis on the surface ultrastructure and surface proteins of Actinobacillus actinomycetemcomitans (Haemophilus actinomycetemcomitans) , 1987, Infection and immunity.

[89]  J. Clark,et al.  The Diabetic Zucker Fatty Rat , 1983, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[90]  F. Sanavi,et al.  Induction of nonspecific tolerance to endotoxins reduces the alveolar bone resorption in ligature-treated rats , 1983, Infection and immunity.

[91]  R. Kenworthy,et al.  Studies of a periodontal tissue lesion in the rat, untreated or treated with chlorhexidine digluconate. , 1981, Journal of clinical periodontology.

[92]  N. Bissada,et al.  Long term effect of systemic tetracycline administration on the severity of induced periodontitis in the rat. , 1979, Journal of periodontology.

[93]  S. Rovin,et al.  The influence of bacteria and irritation in the initiation of periodontal disease in germfree and conventional rats. , 1966, Journal of periodontal research.

[94]  D. Graves,et al.  Porphyromonas gingivalis and E . coli Lipopolysaccharide Exhibit Different Systemic but Similar Local Induction of Inflammatory Markers , 2018 .

[95]  K. Okuda,et al.  Fimbriae-associated genes are biofilm-forming factors in Aggregatibacter actinomycetemcomitans strains. , 2010, The Bulletin of Tokyo Dental College.

[96]  K. Wada,et al.  Roles of oral bacteria in cardiovascular diseases--from molecular mechanisms to clinical cases: Involvement of Porphyromonas gingivalis in the development of human aortic aneurysm. , 2010, Journal of pharmacological sciences.

[97]  T. Sorsa,et al.  Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and laminin-5 gamma2 chain immunolocalization in gingival tissue of endotoxin-induced periodontitis in rats: effects of low-dose doxycycline and alendronate. , 2007, Journal of periodontology.

[98]  T. Sorsa,et al.  Matrix Metalloproteinases, Tissue Inhibitor of Matrix Metalloproteinase-1, and Laminin-5 γ2 Chain Immunolocalization in Gingival Tissue of Endotoxin-Induced Periodontitis in Rats: Effects of Low-Dose Doxycycline and Alendronate. , 2007, Journal of periodontology.

[99]  Louis C Gerstenfeld,et al.  Diabetes causes decreased osteoclastogenesis, reduced bone formation, and enhanced apoptosis of osteoblastic cells in bacteria stimulated bone loss. , 2004, Endocrinology.

[100]  B. Stegenga,et al.  Ultrasound stimulation of maxillofacial bone healing. , 2003, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[101]  J. Carr,et al.  Evaluation of a high-density polytetrafluoroethylene (n-PTFE) membrane as a barrier material to facilitate guided bone regeneration in the rat mandible. , 1995, The Journal of oral implantology.

[102]  Rongkun Liu,et al.  Tumor Necrosis Factor- (cid:1) Mediates Diabetes-Enhanced Apoptosis of Matrix-Producing Cells and Impairs Diabetic Healing , 2006 .