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Research Paper|Volume 13, Issue 5|pp 6945—6956

Silencing of miR-483-5p alleviates postmenopausal osteoporosis by targeting SATB2 and PI3K/AKT pathway

Fujiang Zhao1, Yier Xu2, Yulong Ouyang3, Zhexu Wen3, Guihao Zheng3, Ting Wan3, Guicai Sun4
  • 1Department of Orthopaedics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, China
  • 2Laboratory of Pharmacology, Research and Development Center of Harbin Pharmaceutical Group, Harbin 150025, China
  • 3Medical College of Nanchang University, Nanchang 330006, China
  • 4Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
Received: August 21, 2020Accepted: December 10, 2020Published: February 17, 2021
https://doi.org/10.18632/aging.202552

Copyright: © 2021 Zhao 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

Postmenopausal osteoporosis (PMOP) poses a significant threat to women’s health worldwide. However, detailed molecular mechanism and therapeutic strategy for PMOP remain insufficient. Accumulating evidence suggests that miR-48-5p is implicated in the pathogenesis of osteoporosis. The present study aimed to determine the role and mechanism of miR-483-5p in PMOP. Results from PMOP patients demonstrated that miR-483-5p was up-regulated and SATB2 was down-regulated. Luciferase reporter assay identified SATB2 as a direct target gene of miR-483-5p. Experiments in MC3T3-E1 cells indicated that miR-483-5p mimic markedly inhibited cell viability as well as the expressions of OPG, RUNX2 and BMP2. And miR-483-5p inhibitor, SATB2-overexpressed lentiviruses (Lv-SATB2) or LY294002 (PI3K/AKT inhibitor) significantly reversed the above results. Similarly, PI3K/AKT signaling was activated by miR-483-5p mimic, and was inhibited in miR-483-5p inhibitor, Lv-SATB2 or LY294002 treated cells. In vivo experiments showed that miR-483-5p inhibitor significantly increased the bone mineral density and biomechanical parameters of femurs in ovariectomized (OVX) rats by targeting SATB2. In addition, the osteogenic differentiation and PI3K/AKT signaling were also regulated by miR-483-5p-SATB2 axis. Taken together, our findings indicated that miR-483-5p contributed to the pathogenesis of PMOP by inhibiting SATB2 and activating PI3K/AKT pathway. MiR-483-5p/SATB2 could be selected as a potential therapeutic target for PMOP.