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Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS - PLoS ONE (2015)

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

ABSTRACT
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

No MeSH data available.


Related in: MedlinePlus

Bone Loss in Rats with Experimentally Induced Periodontitis.A) Graph with representative images indicating the amount of area measured between the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) of the first molar after 14 d of experimentally induced periodontal disease (EP) or fictitious induction (sham). Rats were treated with vehicle (water), losartan (50 mg/kg), aliskiren (30 mg/kg) or enalapril (10 mg/kg). All groups n = 5. Statistical significance was determined by ANOVA with interaction analysis and Tukey’s test. Statistical significance (p-value < 0.05) is indicated by * vs. periodontal disease rats treated with water. B to F) Representative images of each of the following: sham group treated with water (B), EP group treated with water (C), aliskiren (D), losartan (E) or enalapril (F). The samples pictured have the following respective CEJ to ABC area: (B) 2.1 mm2, (C) 3.3 mm2, (D) 2.1 mm2, (E) 2.1 mm2, (F) 3.1 mm2.
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pone.0134601.g006: Bone Loss in Rats with Experimentally Induced Periodontitis.A) Graph with representative images indicating the amount of area measured between the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) of the first molar after 14 d of experimentally induced periodontal disease (EP) or fictitious induction (sham). Rats were treated with vehicle (water), losartan (50 mg/kg), aliskiren (30 mg/kg) or enalapril (10 mg/kg). All groups n = 5. Statistical significance was determined by ANOVA with interaction analysis and Tukey’s test. Statistical significance (p-value < 0.05) is indicated by * vs. periodontal disease rats treated with water. B to F) Representative images of each of the following: sham group treated with water (B), EP group treated with water (C), aliskiren (D), losartan (E) or enalapril (F). The samples pictured have the following respective CEJ to ABC area: (B) 2.1 mm2, (C) 3.3 mm2, (D) 2.1 mm2, (E) 2.1 mm2, (F) 3.1 mm2.

Mentions: Since the mRNAs and proteins of RAS components were demonstrated in rat periodontal tissue, pharmacological agents were used to block different components of the RAS in vivo. EP rats (14d) had significant bone loss proximal to the first molar region when treated with vehicle compared to sham rats given vehicle (Fig 6). Notably, treatment with losartan (p-value = 0.03) and aliskiren (p-value = 0.01) for 14d after EP prevented alveolar-bone loss when compared to EP rats given only vehicle (Fig 6). Enalapril treatment had no effect on alveolar-bone loss (Fig 6).


Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS - PLoS ONE (2015)

Bone Loss in Rats with Experimentally Induced Periodontitis.A) Graph with representative images indicating the amount of area measured between the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) of the first molar after 14 d of experimentally induced periodontal disease (EP) or fictitious induction (sham). Rats were treated with vehicle (water), losartan (50 mg/kg), aliskiren (30 mg/kg) or enalapril (10 mg/kg). All groups n = 5. Statistical significance was determined by ANOVA with interaction analysis and Tukey’s test. Statistical significance (p-value < 0.05) is indicated by * vs. periodontal disease rats treated with water. B to F) Representative images of each of the following: sham group treated with water (B), EP group treated with water (C), aliskiren (D), losartan (E) or enalapril (F). The samples pictured have the following respective CEJ to ABC area: (B) 2.1 mm2, (C) 3.3 mm2, (D) 2.1 mm2, (E) 2.1 mm2, (F) 3.1 mm2.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4526652&req=5

pone.0134601.g006: Bone Loss in Rats with Experimentally Induced Periodontitis.A) Graph with representative images indicating the amount of area measured between the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) of the first molar after 14 d of experimentally induced periodontal disease (EP) or fictitious induction (sham). Rats were treated with vehicle (water), losartan (50 mg/kg), aliskiren (30 mg/kg) or enalapril (10 mg/kg). All groups n = 5. Statistical significance was determined by ANOVA with interaction analysis and Tukey’s test. Statistical significance (p-value < 0.05) is indicated by * vs. periodontal disease rats treated with water. B to F) Representative images of each of the following: sham group treated with water (B), EP group treated with water (C), aliskiren (D), losartan (E) or enalapril (F). The samples pictured have the following respective CEJ to ABC area: (B) 2.1 mm2, (C) 3.3 mm2, (D) 2.1 mm2, (E) 2.1 mm2, (F) 3.1 mm2.
Mentions: Since the mRNAs and proteins of RAS components were demonstrated in rat periodontal tissue, pharmacological agents were used to block different components of the RAS in vivo. EP rats (14d) had significant bone loss proximal to the first molar region when treated with vehicle compared to sham rats given vehicle (Fig 6). Notably, treatment with losartan (p-value = 0.03) and aliskiren (p-value = 0.01) for 14d after EP prevented alveolar-bone loss when compared to EP rats given only vehicle (Fig 6). Enalapril treatment had no effect on alveolar-bone loss (Fig 6).

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

ABSTRACT
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

No MeSH data available.


Related in: MedlinePlus