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Research Paper|Volume 13, Issue 20|pp 23652—23671

Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts

Yu Wang1, Runhong Mei1,2, Shimin Hao1, Peng Luo1, Penghao Wang1, Yaser Almatari1, Lei Guo1, Lan Guo1
  • 1Department of Orthopedics, The First Hospital of China Medical University, Shenyang 110001, Liaoning, China
  • 2Department of Orthopaedics, The Fourth Affiliated Hospital, Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
* Equal contribution
Received: January 27, 2021Accepted: September 11, 2021Published: October 28, 2021
https://doi.org/10.18632/aging.203639

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoporosis is a common systemic skeletal metabolism disorder resulting in bone fragility and increased fracture risk. Silent information regulator factor 2 homolog 1 (SIRT1) is crucial in the regulation of several biological processes, including bone metabolism, autophagy, apoptosis, and aging. This study aimed to assess whether the up-regulation of SIRT1 induced by 17beta-estradiol (17β-E2) could promote autophagy and inhibit apoptosis in osteoblasts via the AMPK-mTOR and FOXO3a pathways, respectively. The study found that 17β-E2 (10-6 M) administration induced the up-regulation of SIRT1 in osteoblasts. Up-regulation of SIRT1 induced by 17β-E2 increased the expression level of LC3, Beclin-1, Bcl-2, p-AMPK, FOXO3a but decreased caspase-3 and p-mTOR expression, and then promoted autophagy and inhibited apoptosis. More autophagosomes were observed under a transmission electron microscope (TEM) in 17β-E2 and SRT1720 (a selective SIRT1 activator) co-treated group. When Ex527 (a SIRT1-specific inhibitor) was pretreated, the reversed changes were observed. Taken together, our findings demonstrated that the up-regulation of SIRT1 induced by 17β-E2 could promote autophagy via the AMPK-mTOR pathway and inhibit apoptosis via the FOXO3a activation in osteoblasts, and SIRT1 might become a more significant target in osteoporosis treatment.