Alisquireno modula o metabolismo ósseo em camundongos diabéticos com doença periodontal
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Data
2022-12-21
Autores
Ribeiro, Bianca da Silva [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O sistema renina-angiotensina (SRA), além da inflamação, está associado à remodelação óssea pela ação da angiotensina. No presente estudo avaliamos o papel da renina no metabolismo ósseo mandibular em camundongos normais (N) e diabéticos (D) com Doença Periodontal (DP). Usamos camundongos Balb/c machos e o diabetes foi induzido por injeção intraperitoneal de estreptozotocina (STZ). A DP foi induzida pela inserção de uma ligadura bilateral nos primeiros molares inferiores. O tratamento foi administrado concomitantemente por 15 dias na dose de 50 mg/kg de Alisquireno (Alisk). Os animais foram eutanasiados e as mandíbulas coletadas para análise morfológica, expressão gênica, marcação tecidual e produção de citocinas pró-inflamatórias. A análise morfológica mostrou perda óssea acentuada em ambos os grupos, com piora da perda óssea no grupo D tratado com Alisk (DAlisk+PD). A produção de citocinas pró-inflamatórias teve um aumento na expressão de IL1-β em ambos os grupos com DP (NPD e DPD), um aumento na expressão de IL-6 apenas em camundongos D com DP (DPD), e um aumento na expressão de TNF-α em camundongos N, mas não em camundongos D. O tratamento com Alisk diminuiu significativamente a produção de IL-6 em camundongos D e IL-1β em ambos os grupos. A expressão gênica dos fatores de formação óssea mostrou diminuição de Alp, Col1a1 e Ocn, e aumento de Bmp2 e Opn no grupo DPD. O tratamento com Alisk não alterou Alp, Col1a1 e Ocn, mas diminuiu Opn. No grupo N com DP (NPD) houve aumento na expressão de Col1a1 e Bsp. O tratamento com Alisk diminuiu a expressão desses marcadores (NAlisk+PD). A expressão dos marcadores de reabsorção óssea Trap, Mmp9, Oscar e Socs1 foi maior no grupo NPD, enquanto no grupo DPD houve aumento na expressão de Trap, Mmp9 Ctsk e Oscar, e observamos o mesmo resultado no grupo DPD em relação à marcação tecidual. O tratamento no grupo DALisk+PD, Alisk aumentou significativamente a expressão de Oscar e Socs1. No grupo NAlisk+PD, Alisk reduziu Trap e Mmp2. Em conclusão, nosso estudo sugere que a renina tem um papel protetor no metabolismo ósseo em animais D com DP, uma vez que sua inibição por Alisk causou uma deterioração significativa no metabolismo ósseo nesses animais, já que na ausência de renina foi observado um aumento de Oscar. e SOCS-1, bem como IL-6 e IL-1β que são citocinas osteoclastogênicas.
In addition to inflammation, the renin-angiotensin system (RAS) is associated with bone remodeling through the action of angiotensin. In the present study, we evaluated the role of renin in mandibular bone metabolism in normal (N) and diabetic (D) mice with Periodontal Disease (PD). We used male Balb/c mice and diabetes was induced by peritoneal injection of streptozotocin (STZ). PD was induced by the insertion of a bilateral ligature in the lower first molars. Treatment was administered concomitantly for 15 days at a dose of 50 mg/kg of Aliskiren (Alisk). Animals were euthanized and the mandibles were collected for morphological analysis, gene expression, tissue labeling, and production of pro-inflammatory cytokines. Morphological analysis showed a marked bone loss in both groups, with worsening bone loss in group D treated with Alisk (DAlisk+PD). The production of pro-inflammatory cytokines had an increase in the expression of IL1-β in both groups with PD (NPD and DPD), an increase in the expression of IL-6 only in D mice with PD (DPD), and an increase in the TNF-α expression in N mice, but not in D mice. Treatment with Alisk significantly decreased IL-6 production in D and IL-1β mice in both groups. The gene expression of bone formation factors showed a decrease in Alp, Col1a1, and Ocn, and an increase in Bmp2 and Opn in the DPD group. Treatment with Alisk did not change Alp, Col1a1, and Ocn, but decreased Opn. In group N with PD (NPD), there was an increase in the expression of Col1a1 and Bsp. Treatment with Alisk decreased the expression of these markers (NAlisk+PD). The expression of bone resorption markers Trap, Mmp9, Oscar, and Socs1 was higher in the NPD group, while in the DPD group, there was an increase in the expression of Trap, Mmp9 Ctsk, and Oscar, and we observed the same result in the DPD group in relation to tissue labeling. Treatment in the DALisk+PD, Alisk group significantly increased the expression of Oscar and Socs1. In the NAlisk+PD group, Alisk reduced Trap and Mmp2. In conclusion, our study suggests that renin has a protective role in bone metabolism in D animals with PD since its inhibition by Alisk caused a significant deterioration in bone metabolism in these animals since in the absence of renin an increase in Oscar was observed. and SOCS-1, as well as IL-6 and IL-1β which are osteoclastogenic cytokines.
In addition to inflammation, the renin-angiotensin system (RAS) is associated with bone remodeling through the action of angiotensin. In the present study, we evaluated the role of renin in mandibular bone metabolism in normal (N) and diabetic (D) mice with Periodontal Disease (PD). We used male Balb/c mice and diabetes was induced by peritoneal injection of streptozotocin (STZ). PD was induced by the insertion of a bilateral ligature in the lower first molars. Treatment was administered concomitantly for 15 days at a dose of 50 mg/kg of Aliskiren (Alisk). Animals were euthanized and the mandibles were collected for morphological analysis, gene expression, tissue labeling, and production of pro-inflammatory cytokines. Morphological analysis showed a marked bone loss in both groups, with worsening bone loss in group D treated with Alisk (DAlisk+PD). The production of pro-inflammatory cytokines had an increase in the expression of IL1-β in both groups with PD (NPD and DPD), an increase in the expression of IL-6 only in D mice with PD (DPD), and an increase in the TNF-α expression in N mice, but not in D mice. Treatment with Alisk significantly decreased IL-6 production in D and IL-1β mice in both groups. The gene expression of bone formation factors showed a decrease in Alp, Col1a1, and Ocn, and an increase in Bmp2 and Opn in the DPD group. Treatment with Alisk did not change Alp, Col1a1, and Ocn, but decreased Opn. In group N with PD (NPD), there was an increase in the expression of Col1a1 and Bsp. Treatment with Alisk decreased the expression of these markers (NAlisk+PD). The expression of bone resorption markers Trap, Mmp9, Oscar, and Socs1 was higher in the NPD group, while in the DPD group, there was an increase in the expression of Trap, Mmp9 Ctsk, and Oscar, and we observed the same result in the DPD group in relation to tissue labeling. Treatment in the DALisk+PD, Alisk group significantly increased the expression of Oscar and Socs1. In the NAlisk+PD group, Alisk reduced Trap and Mmp2. In conclusion, our study suggests that renin has a protective role in bone metabolism in D animals with PD since its inhibition by Alisk caused a significant deterioration in bone metabolism in these animals since in the absence of renin an increase in Oscar was observed. and SOCS-1, as well as IL-6 and IL-1β which are osteoclastogenic cytokines.
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Palavras-chave
Doenças periodontais, Diabetes mellitus, Ossos, Sistema renina-angiotensina, Periodontal diseases