Platelet-Activating Factor Receptor Blockade Ameliorates Aggregatibacter actinomycetemcomitans-Induced Periodontal Disease in Mice

Madeira, Mila Fernandes Moreira; Queiroz-Junior, Celso Martins; Costa, Graciela Mitre; Werneck, Silvia Maria Cordeiro; Cisalpino, Daniel; Garlet, Gustavo; Teixeira, Mauro Martins; Silva, Tarcı́lia Aparecida; Souza, Daniele G.

doi:10.1128/iai.01046-13

Cited by 14 publications

(26 citation statements)

References 49 publications

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“…Immediately after the mice were killed, knee cavities were washed with PBS and the total number of leukocytes was estimated in a Neubauer cell count chamber. Periarticular tissues were removed from the joint and used in enzymatic assays for detection of N ‐acetylglucosaminidase (NAG) activity, an enzyme marker of machrophages, as described previously . Samples were assayed for NAG by measuring the change in absorbance at 405 nm using p‐nitrophenyl‐ N ‐acetyl‐β‐ d ‐glucosaminide (Sigma‐Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection‐induced and arthritis‐associated alveolar bone loss

Queiroz-Júnior

Silveira

Oliveira

et al. 2015

J of Periodontal Research

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Section: Methodsmentioning

confidence: 99%

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection‐induced and arthritis‐associated alveolar bone loss

Queiroz-Júnior

Silveira

Oliveira

et al. 2015

J of Periodontal Research

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“…Placement of ligatures is one of the most widely used models in periodontal research (14). Other models include the localized injection of the pathogen or a bacterial component such as lipopolysaccharide into the palatal gingival tissue (15)(16)(17)(18)(19). Furthermore, periodontal disease in mice has been commonly induced by inoculating the pathogen with a microsyringe or micropipette or by oral gavage, respectively (20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

“…It has been also recognized that the host response plays an important role in periodontal tissue breakdown. Several host factors, including interferon gamma (22), Toll-like receptor 4 (24), myeloid differentiation primary-response protein 88 (17), p55 tumor necrosis factor alpha (TNF-␣) receptor (21), chemokine receptors CCR1/5 (25,26), macrophage migration inhibitory factor (15), platelet-activator factor receptor (18), and sphingosine kinase 1 (19), have been found to contribute to A. actinomycetemcomitans-induced periodontitis in mice. In contrast, Toll-like receptor 2 has been reported to be important for controlling A. actinomycetemcomitans infection (36), and the antimicrobial agent lactoferrin has been reported to inhibit A. actinomycetemcomitans-induced osteoclastogenesis (27).…”

Section: Figmentioning

confidence: 99%

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

et al. 2017

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Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of periodontitis with severe alveolar bone destruction. The role of host factors such as reactive oxygen and nitrogen intermediates in periodontal A. actinomycetemcomitans infection and progression to periodontitis is still ill-defined. Therefore, this study aimed to analyze the role of NADPH oxidase and inducible nitric oxide synthase (iNOS) in a murine model of A. actinomycetemcomitans-induced periodontitis. NADPH oxidase-deficient (gp91 phox knockout [KO]), iNOS-deficient (iNOS KO), and C57BL/6 wild-type mice were orally infected with A. actinomycetemcomitans and analyzed for bacterial colonization at various time points. Alveolar bone mineral density and alveolar bone volume were quantified by three-dimensional microcomputed tomography, and the degree of tissue inflammation was calculated by histological analyses. At 5 weeks after infection, A. actinomycetemcomitans persisted at significantly higher levels in the murine oral cavities of infected gp91 phox KO mice than in those of iNOS KO and C57BL/6 mice. Concomitantly, alveolar bone mineral density was significantly lower in all three infected groups than in uninfected controls, but with the highest loss of bone density in infected gp91 phox KO mice. Only infected gp91 phox KO mice revealed significant loss of alveolar bone volume and enhanced inflammatory cell infiltration, as well as an increased number of osteoclasts. Our results indicate that NADPH oxidase is important to control A. actinomycetemcomitans infection in the murine oral cavity and to prevent subsequent alveolar bone destruction and osteoclastogenesis.

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“…Since its discovery, the pleiotropic and potential biological effects of PAF have been extensively reported [10][11][12]. In the bone field, although several experimental studies report the direct effects of PAF on osteoclasts [15,16,25], the most convincing evidence of PAF's role in the pathogenesis of osteoporosis was provided by [17]. In their study, TNF-α and IL-1, which are cytokines increased after ovarian dysfunction, elevate PAF production in osteoclasts via the activation of acetyl-coenzyme A:lyso-PAF acetyltransferase.…”

Section: Characteristicmentioning

confidence: 99%

Higher plasma platelet-activating factor levels are associated with increased risk of vertebral fracture and lower bone mineral density in postmenopausal women

Kim

Ahn

et al. 2014

J Bone Miner Metab

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Despite experimental and animal evidence showing the detrimental effects of platelet-activating factor (PAF) on bone metabolism, there are no clinical studies relating PAF to osteoporosis-related phenotypes. This case-control study investigates the association between plasma PAF, osteoporotic vertebral fracture (VF), and bone mineral density (BMD) in postmenopausal Korean women. Among 474 eligible women not taking any drug or having any disease that could affect bone metabolism, we identified 73 cases defined as subjects with radiological VF. The controls were randomly selected from the remaining 401 subjects and matched 1:1 to cases in terms of both age and body mass index (BMI). Lateral thoracolumbar radiographs, BMD, and plasma PAF levels were determined for all subjects. Postmenopausal women with VF demonstrated 34.6 % higher plasma PAF levels than subjects without VF after adjusting for age, BMI, smoking habits, alcohol intake, regular exercise, and parental history of osteoporotic fractures (P = 0.021). Multiple logistic regression analyses revealed that the odds ratio for VF linearly increased across increasing PAF quartiles (P for trend = 0.040) and the odds for VF were 2.88-fold higher in subjects in the highest quartile in comparison with those in the lowest quartile (95 % CI 1.04-8.01). Plasma PAF levels were inversely correlated with BMD at various sites (γ = -0.253 to -0.176, P = 0.003-0.041). These findings suggest that plasma PAF may be a potential biomarker for predicting poor bone health in postmenopausal women.

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Platelet-Activating Factor Receptor Blockade Ameliorates Aggregatibacter actinomycetemcomitans-Induced Periodontal Disease in Mice

Cited by 14 publications

References 49 publications

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection‐induced and arthritis‐associated alveolar bone loss

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection‐induced and arthritis‐associated alveolar bone loss

NADPH Oxidase Contributes to Resistance against Aggregatibacter actinomycetemcomitans-Induced Periodontitis in Mice

Higher plasma platelet-activating factor levels are associated with increased risk of vertebral fracture and lower bone mineral density in postmenopausal women

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