Department of Gynecology and Obstetrics, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Ultrasonic Diagnosis and Treatment in Obstetrics and Gynecology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Climacteric. 2020 Aug;23(4):404-409. doi: 10.1080/13697137.2020.1758057. Epub 2020 May 15.
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. 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. 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. 17β-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.
本研究旨在通过 Sirtuin-1/核转录因子-κB/基质金属蛋白酶-8（Sirt1/NF-κB/MMP-8）通路探讨 17β-雌二醇对成骨细胞功能的有益作用。从小鼠胎鼠颅骨中获得原代成骨细胞，并用或不用 17β-雌二醇处理细胞。我们首先检测了 17β-雌二醇对成骨细胞功能的影响。然后，在成骨细胞用 17β-雌二醇处理后，测定雌激素受体-α（ERα）、Sirt1、NF-κB 和 MMP-8 的变化。在补充 17β-雌二醇时，使用成骨细胞中的 Sirt1 敲低来进一步测量 NF-κB 和 MMP-8 的变化，并观察细胞功能。在原代成骨细胞中，暴露于 17β-雌二醇可提高细胞活力，并增加骨形成生物标志物的水平，包括骨钙素、骨保护素（OPG）、I 型前胶原 N 端前肽（P1NP）和碱性磷酸酶（ALP）。此外，17β-雌二醇补充剂激活 ERα 和 Sirt1 的表达，并抑制 NF-κB 和 MMP-8 的表达。此外，这些由 17β-雌二醇诱导的作用通过在小鼠原代成骨细胞中敲低 Sirt1 而被逆转。17β-雌二醇替代疗法可能通过 Sirt1/NF-κB/MMP-8 通路改善成骨细胞功能来治疗绝经后骨质疏松症。
