Efeito do tratamento sistêmico com tanshinona na modulação da doença periodontal experimental: estudo em camundongos
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Data
2022-03-30
Autores
Pavanelli, Angélica Letícia Reis [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A periodontite é uma doença inflamatória crônica, altamente prevalente, de etiologia multicausal e que se desenvolve como resultado de complexas interações parasita-hospedeiro. Se não tratada, ela resulta na reabsorção do tecido conjuntivo mineralizado e não mineralizado ao redor dos dentes. O processo inflamatório próximo ao esqueleto leva a um fenótipo clínico de perda óssea, observado em diversas patologias, como artrose, artrite reumatoide e doença periodontal (DP). Esse processo é dependente da diferenciação e atividade de osteoclastos, as células responsáveis por reabsorver o tecido ósseo. Desta forma, a inibição da diferenciação ou da atividade dessas células é uma estratégia viável para o controle da reabsorção óssea. A Tanshinona é uma substância natural da Salvia miltiorrhiza (Danshen) que emergiu recentemente como fármacos promissores na redução do fenótipo osteoporótico em camundongos. Tais compostos são capazes de inibir especificamente a atividade colagenolítica da catepsina K, enzima secretada pelos osteoclastos que participa da degradação da fase orgânica da matriz óssea, sem interferir na diferenciação de osteoclastos. Porém, os efeitos desses fármacos na inibição da perda óssea causada por inflamação não estão bem elucidados. Sendo assim, o presente estudo apresenta como objetivo avaliar os efeitos desses fármacos como tratamento sistêmico na modulação da DP experimental. Para isto, foram utilizados camundongos C57BL6/J, machos distribuídos em 4 grupos experimentais (n=10), conforme descritos: grupo doença periodontal (DP), grupo tanshinona TIIA (TIIA), grupo tanshinona T06 (T06), e o Grupo Controle (C). Os animais dos grupos DP, TIIA e T06 receberam indução experimental de DP por meio da colocação de ligaduras. As tanshinonas foram administradas diariamente por 10 dias para o grupo TIIA e T06, e o Grupo DP obteve o tratamento com solução veículo (água) por meio de gavagem oral. Após esse período os animais foram eutanasiados. As amostras obtidas foram utilizadas para avaliação do processo imuno-inflamatório presente no tecido gengival, por meio de análise de RT-PCR em tempo real. A avaliação da perda óssea alveolar foi avaliada por microtomografia computadorizada (μCT). O grupo DP apresentou significante perda óssea alveolar, no período de 10 dias, comparado ao grupo controle e os demais grupos TIIA e T06. Houve aumento significante na expressão gênica do mediador inflamatório IL-1b e na catepsina K envolvida no processo de osteoclastogênese para o grupo DP em relação ao grupo controle. Essas expressões se mostraram menores nos grupos TIIA e T06 comparados ao grupo DP. Com base nos achados do presente estudo, sugere-se que as tanshinonas (TIIA e T06) são estratégias promissoras na modulação da DP experimental em camundongos.
Periodontitis is a highly prevalent chronic inflammatory disease of multicausal etiology that develops as a result of complex host parasite interactions. If left untreated, it results in the resorption of mineralized and non-mineralized connective tissue of the teeth. The inflammatory process near the skeleton leads to a clinical phenotype of bone loss, observed in several pathologies, such as arthrosis, rheumatoid arthritis and periodontal disease (PD). This process is dependent on the activity of osteoclasts, the cells responsible for the resorption of the bone tissue. This process is dependent on the differentiation and activity of osteoclasts, the cells responsible for resorbing bone tissue. Thus, inhibition of differentiation or activity of these cells is a viable strategy to control bone resorption. Tanshinone is a natural substance from Salvia miltiorrhiza (Danshen) that has appeared as promising drugs in reducing the osteoporotic phenotype in mice. Such compounds are capable of specifically inhibiting the collagenolytic activity of cathepsin K, an enzyme secreted by osteoclasts that participates in the degradation of the organic phase of the bone matrix, without interfering with osteoclast differentiation. However, the effects of these drugs in inhibiting bone loss caused by inflammation are not well understood. Therefore, the present study aims to evaluate the effects of these drugs as a systemic treatment in the modulation of experimental PD. For this, C57BL6/J male mice were distributed into 4 experimental groups (n=10), as described: periodontal disease (PD) group, TIIA tanshinone group (TIIA), T06 tanshinone group (T06), and the control Group. (C). The animals in the PD, TIIA and T06 groups received experimental induction of PD through the placement of ligatures. The tanshinones were administered daily for 10 days for the TIIA and T06 groups, and the DP group was treated with vehicle solution (water) through oral gavage. After this period, the animals were euthanized. The samples obtained were used to evaluate the immuno-inflammatory process present in the gingival tissue by means of real-time RT-PCR analysis. Assessment of alveolar bone loss was evaluated by micro computed tomography (μCT). The PD group showed significant alveolar bone loss within 10 days, compared to the control group and the other TIIA and T06 groups. There was a significant increase in the gene expression of the inflammatory mediator IL-1b and in the cathepsin K involved in the osteoclastogenesis process for the PD group compared to the control group. These expressions were lower in the TIIA and T06 groups compared to the PD group. Based on the findings of the present study, it is suggested that tanshinones (TIIA and T06) are a promising strategy in modulating experimental periodontal disease in mice.
Periodontitis is a highly prevalent chronic inflammatory disease of multicausal etiology that develops as a result of complex host parasite interactions. If left untreated, it results in the resorption of mineralized and non-mineralized connective tissue of the teeth. The inflammatory process near the skeleton leads to a clinical phenotype of bone loss, observed in several pathologies, such as arthrosis, rheumatoid arthritis and periodontal disease (PD). This process is dependent on the activity of osteoclasts, the cells responsible for the resorption of the bone tissue. This process is dependent on the differentiation and activity of osteoclasts, the cells responsible for resorbing bone tissue. Thus, inhibition of differentiation or activity of these cells is a viable strategy to control bone resorption. Tanshinone is a natural substance from Salvia miltiorrhiza (Danshen) that has appeared as promising drugs in reducing the osteoporotic phenotype in mice. Such compounds are capable of specifically inhibiting the collagenolytic activity of cathepsin K, an enzyme secreted by osteoclasts that participates in the degradation of the organic phase of the bone matrix, without interfering with osteoclast differentiation. However, the effects of these drugs in inhibiting bone loss caused by inflammation are not well understood. Therefore, the present study aims to evaluate the effects of these drugs as a systemic treatment in the modulation of experimental PD. For this, C57BL6/J male mice were distributed into 4 experimental groups (n=10), as described: periodontal disease (PD) group, TIIA tanshinone group (TIIA), T06 tanshinone group (T06), and the control Group. (C). The animals in the PD, TIIA and T06 groups received experimental induction of PD through the placement of ligatures. The tanshinones were administered daily for 10 days for the TIIA and T06 groups, and the DP group was treated with vehicle solution (water) through oral gavage. After this period, the animals were euthanized. The samples obtained were used to evaluate the immuno-inflammatory process present in the gingival tissue by means of real-time RT-PCR analysis. Assessment of alveolar bone loss was evaluated by micro computed tomography (μCT). The PD group showed significant alveolar bone loss within 10 days, compared to the control group and the other TIIA and T06 groups. There was a significant increase in the gene expression of the inflammatory mediator IL-1b and in the cathepsin K involved in the osteoclastogenesis process for the PD group compared to the control group. These expressions were lower in the TIIA and T06 groups compared to the PD group. Based on the findings of the present study, it is suggested that tanshinones (TIIA and T06) are a promising strategy in modulating experimental periodontal disease in mice.
Descrição
Palavras-chave
Catepsina K, Doenças periodontais, Perda do osso alveolar, Osteoclastos, Cathepsin K, Periodontal diseases, Alveolar Bone Loss, Osteoclasts