17β-Estradiol improves osteoblastic cell function through the Sirt1/NF-κB/MMP-8 pathway

Abstract

<b>Objective:</b> This study aims to investigate the beneficial effects of 17β-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.<b>Methods:</b> Mouse primary osteoblasts were obtained from neonatal mouse calvaria, and the cells were treated with or without 17β-estradiol. We first detected the effect of 17β-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 17β-estradiol. During supplementation with 17β-estradiol, knockdown of Sirt1 in osteoblasts was used to further measure the changes of NF-κB and MMP-8 and observe the cell function.<b>Results:</b> In primary osteoblastic cells, exposure to 17β-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, 17β-estradiol supplement activated ERα and Sirt1 expression and inhibited NF-κB and MMP-8 expression. Moreover, these effects induced by 17β-estradiol were reversed by knockdown of Sirt1 in mouse primary osteoblasts.<b>Conclusion:</b> 17β-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.