Limits...
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

ACE Activity and Generation of Renin-Angiotensin System Components from Human Gingiva.A) Fluorimetric assay of ACE activity in gingiva homogenates from donors with healthy gingiva (open bar), gingivitis (gray bar) or periodontitis (black bar). The means were compared using a 1-way ANOVA and Tukey’s test. * indicates significant difference from healthy group. B to E) HPLC assay of homogenates from all three groups after incubation with either captopril (10μM), chymostatin (100μM), both captopril (10μM) and chymostatin (100μM), or nothing. * indicates significant differences from all other healthy groups (open bars); † indicates significant differences from all other gingivitis groups (gray bars); ‡ indicates significant differences from all other periodontitis groups (black bars); unless otherwise noted with brackets (e.g. Fig 3C). B) Indicates the amount of Ang II formed when incubated with Ang I. C) Indicates the amount of Ang 1–9 formed when incubated with Ang I. D) Indicates the amount of Ang 1–7 formed when incubated with Ang I. E) Indicates the amount of Ang 1–7 formed when incubated with Ang II.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526652&req=5

pone.0134601.g003: ACE Activity and Generation of Renin-Angiotensin System Components from Human Gingiva.A) Fluorimetric assay of ACE activity in gingiva homogenates from donors with healthy gingiva (open bar), gingivitis (gray bar) or periodontitis (black bar). The means were compared using a 1-way ANOVA and Tukey’s test. * indicates significant difference from healthy group. B to E) HPLC assay of homogenates from all three groups after incubation with either captopril (10μM), chymostatin (100μM), both captopril (10μM) and chymostatin (100μM), or nothing. * indicates significant differences from all other healthy groups (open bars); † indicates significant differences from all other gingivitis groups (gray bars); ‡ indicates significant differences from all other periodontitis groups (black bars); unless otherwise noted with brackets (e.g. Fig 3C). B) Indicates the amount of Ang II formed when incubated with Ang I. C) Indicates the amount of Ang 1–9 formed when incubated with Ang I. D) Indicates the amount of Ang 1–7 formed when incubated with Ang I. E) Indicates the amount of Ang 1–7 formed when incubated with Ang II.

Mentions: Since no differences were observed between the mRNA of AT1Rs and AT2Rs between healthy and diseased tissue, the activity of ACE and RAS components were measured in the healthy, gingivitis and periodontitis groups. Fluorometric analysis indicated increased ACE activity in gingiva samples from volunteers with gingivitis compared to the healthy group (p-value = 0.02, Fig 3A). However, gingivae from volunteers with periodontitis had moderate ACE activity and were not significantly different from either healthy or gingiva homogenates (p-value > 0.05).


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)

ACE Activity and Generation of Renin-Angiotensin System Components from Human Gingiva.A) Fluorimetric assay of ACE activity in gingiva homogenates from donors with healthy gingiva (open bar), gingivitis (gray bar) or periodontitis (black bar). The means were compared using a 1-way ANOVA and Tukey’s test. * indicates significant difference from healthy group. B to E) HPLC assay of homogenates from all three groups after incubation with either captopril (10μM), chymostatin (100μM), both captopril (10μM) and chymostatin (100μM), or nothing. * indicates significant differences from all other healthy groups (open bars); † indicates significant differences from all other gingivitis groups (gray bars); ‡ indicates significant differences from all other periodontitis groups (black bars); unless otherwise noted with brackets (e.g. Fig 3C). B) Indicates the amount of Ang II formed when incubated with Ang I. C) Indicates the amount of Ang 1–9 formed when incubated with Ang I. D) Indicates the amount of Ang 1–7 formed when incubated with Ang I. E) Indicates the amount of Ang 1–7 formed when incubated with Ang II.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134601.g003: ACE Activity and Generation of Renin-Angiotensin System Components from Human Gingiva.A) Fluorimetric assay of ACE activity in gingiva homogenates from donors with healthy gingiva (open bar), gingivitis (gray bar) or periodontitis (black bar). The means were compared using a 1-way ANOVA and Tukey’s test. * indicates significant difference from healthy group. B to E) HPLC assay of homogenates from all three groups after incubation with either captopril (10μM), chymostatin (100μM), both captopril (10μM) and chymostatin (100μM), or nothing. * indicates significant differences from all other healthy groups (open bars); † indicates significant differences from all other gingivitis groups (gray bars); ‡ indicates significant differences from all other periodontitis groups (black bars); unless otherwise noted with brackets (e.g. Fig 3C). B) Indicates the amount of Ang II formed when incubated with Ang I. C) Indicates the amount of Ang 1–9 formed when incubated with Ang I. D) Indicates the amount of Ang 1–7 formed when incubated with Ang I. E) Indicates the amount of Ang 1–7 formed when incubated with Ang II.
Mentions: Since no differences were observed between the mRNA of AT1Rs and AT2Rs between healthy and diseased tissue, the activity of ACE and RAS components were measured in the healthy, gingivitis and periodontitis groups. Fluorometric analysis indicated increased ACE activity in gingiva samples from volunteers with gingivitis compared to the healthy group (p-value = 0.02, Fig 3A). However, gingivae from volunteers with periodontitis had moderate ACE activity and were not significantly different from either healthy or gingiva homogenates (p-value > 0.05).

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