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Climacteric ; 23(4): 404-409, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32410477

RESUMO

Objective: This study aims to investigate the beneficial effects of 17ß-estradiol supplementation on the function of osteoblastic cells through the Sirtuin-1/nuclear transcription factor-κB/matrix metalloproteinase-8 (Sirt1/NF-κB/MMP-8) pathway.Methods: Mouse primary osteoblasts were obtained from neonatal mouse calvaria, and the cells were treated with or without 17ß-estradiol. We first detected the effect of 17ß-estradiol on the function of osteoblastic cells. Then, the changes in estrogen receptor-α (ERα), Sirt1, NF-κB, and MMP-8 were determined after the osteoblasts were treated with 17ß-estradiol. During supplementation with 17ß-estradiol, knockdown of Sirt1 in osteoblasts was used to further measure the changes of NF-κB and MMP-8 and observe the cell function.Results: In primary osteoblastic cells, exposure to 17ß-estradiol improved cell viability and increased the levels of bone formation biomarkers, including osteocalcin, osteoprotegerin (OPG), procollagen type 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). In addition, 17ß-estradiol supplement activated ERα and Sirt1 expression and inhibited NF-κB and MMP-8 expression. Moreover, these effects induced by 17ß-estradiol were reversed by knockdown of Sirt1 in mouse primary osteoblasts.Conclusion: 17ß-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.


Assuntos
Estradiol/farmacologia , Metaloproteinase 8 da Matriz/metabolismo , NF-kappa B/metabolismo , Osteoblastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Fosfatase Alcalina/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Camundongos , Modelos Animais , Osteoblastos/metabolismo , Osteocalcina/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoprotegerina/efeitos dos fármacos , Fragmentos de Peptídeos/efeitos dos fármacos , Pró-Colágeno/efeitos dos fármacos
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