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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 17β-Estradiol replacement therapy may treat postmenopausal osteoporosis by improving osteoblastic cell function via the Sirt1/NF-κB/MMP-8 pathway.

摘要

目的：本研究旨在探索补充17β雌二醇有益于通过Sirtuin-1/核转录因子-κB/基质金属肽酶8 (Sirt1/NF-κB/MMP-8)通路, 提高成骨细胞的功能

方法：从新生小鼠的颅骨中获得小鼠原代成骨细胞, 分别添加17β雌二醇或者不添加17β雌二醇处理。我们首先检测17β雌二醇对成骨细胞功能的影响。随后检测经过17β雌二醇处理后的成骨细胞的雌激素受体α（ERα)、Sirt 1、NF-κB和MMP-8的变化。敲除成骨细胞的Sirt1基因, 予以17β雌二醇处理, 进一步检测NF-κB和MMP-8的改变, 观察细胞功能。

结果：在原代成骨细胞中, 17β雌二醇提高了细胞的存活率, 并增加了骨形成的生物标志物的水平, 包括骨钙蛋白、护骨素、1型前胶原氨基端延长肽（P1NP）和碱性磷酸酶（ALP)。此外, 补充17β雌二醇激活了ERα和Sirt1的表达, 抑制NF-κB和MMP-8的表达。此外, 在敲除Sirt1的原代成骨细胞中17β雌二醇诱导的结果相反。

结论：17β雌二醇替代治疗可能治疗绝经后骨质疏松症, 通过Sirt1/NF-κB/MMP-8信号通路。

, 提高成骨细胞的细胞功能。

Keywords:

• Postmenopausal osteoporosis
• 17β-estradiol
• osteoblasts
• matrix metalloproteinase-8
• Sirtuin-1
• nuclear transcription factor-κB

Potential conflict of interest

No potential conflict of interest was reported by the authors.

Source of funding

Nil.