Resveratrol promotes bone mass in ovariectomized rats and the SIRT1 rs7896005 SNP is associated with bone mass in women during perimenopause and early postmenopause

Abstract

Objective

This study aimed to examine the effects of SIRT1 agonist resveratrol on bone mass in ovariectomized (OVX) rats and the SIRT1 single-nucleotide polymorphism (SNP) rs7896005 on bone mass in women during menopause and early postmenopause.

Methods

An animal experiment was conducted on rats that were sham-operated (SHAM), OVX or OVX and different administered doses of resveratrol. Serum markers and femur microstructure and staining were assessed. A cross-sectional study was conducted in women undergoing menopause. SIRT1 protein and SIRT1 SNP rs7896005 were evaluated.

Results

OVX rats administered resveratrol, especially high doses, showed lower bone loss than OVX rats. Serum osteoprotegerin (OPG) and femur SIRT1, β-catenin and bone mineral density (BMD) were significantly increased, whereas receptor activator of NF-κB ligand (RANKL) was significantly decreased. Serum SIRT1 levels were significantly lower in women with low bone mass (p < 0.01). Women with the CA genotype of rs7896005 had lower bone mass than those with the CC genotype. The A allele showed a significant negative effect on bone loss risk (odds ratio = 3.48; p = 0.025).

Conclusions

Resveratrol stimulated SIRT1 expression and Wnt/β-catenin signaling to promote bone mass in rat femurs. Among women in perimenopause and early postmenopause, SIRT1 protected bone mass, and the A allele of SIRT1 rs7896005 was a risk factor for reduced bone mass.

摘要

目的：本研究旨在研究SIRT1激动剂白藜芦醇对卵巢切除（OVX）大鼠骨量的影响以及SIRT1单核苷酸多态性（SNP）rs7896005对女性绝经期和绝经后早期骨量的影响。

方法：对假手术（SHAM）、OVX或OVX给不同剂量的白藜芦醇的大鼠进行了动物实验。评估了血清标志物和股骨微观结构和染色。对处于绝经期女性进行了一项横断面研究。对SIRT1蛋白和SIRT1 SNP rs7896005进行了评估。

结果：给予白藜芦醇的OVX大鼠, 尤其是高剂量的白藜芦醇, 显示出比OVX大鼠更低的骨质流失。血清中骨蛋白（OPG）和股骨SIRT1、β-catenin和骨矿物质密度（BMD）明显增加, 而NF-κB配体的受体激活剂（RANKL）则明显减少。低骨量女性的血清SIRT1水平明显降低（p < 0.01）。rs7896005的CA基因型的女性比CC基因型的女性骨量低。A等位基因对骨质流失风险显示出显著的负作用（优势比=3.48；p=0.025）。

结论：白藜芦醇刺激SIRT1的表达和Wnt/β-catenin信号, 促进大鼠股骨骨量。在围绝经期和绝经后早期的女性中, SIRT1保护骨量, 而SIRT1 rs7896005的A等位基因是骨量减少的危险因素。

Keywords:

• SIRT1
• resveratrol
• β-catenin
• menopause
• bone mass
• single-nucleotide polymorphism

Acknowledgements

The authors thank all team members and the women who agreed to participate in this study. The funder had no role on the study design, data collection and analysis, animal experiments and writing the manuscript in this study.

Potential conflict of interest

The authors have no potential conflicts of interest.

Ethics approval and consent to participate

All of the participants provided informed written consent before their participation. Ethical approval for this study was granted by the ethics committee of Hangzhou First People’s Hospital (reference number 2015-001-03). The animal care and experimental procedures were in accordance with the institutional guidelines for laboratory animals established by the Institutional Animal Care and Use Committee of Zhejiang Chinese Medical University. All experimental procedures conformed to the European Guidelines for the care and use of Laboratory Animals (directive 2010/63/EU).

Additional information

Funding

The study is supported by grants from Science Technology Department of Zhejiang Province [No. 2014C03044-1].