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Research Paper|Volume 14, Issue 2|pp 892—906

The effect of QiangGuYin on osteoporosis through the AKT/mTOR/autophagy signaling pathway mediated by CKIP-1

Yifeng Yuan1, Jiangang Sun1, Hang Zhou1, Shen Wang1, Caijian He1, Tianpeng Chen1, Mouhao Fang1, Shaohua Li1, Shifa Kang1, Xiaosheng Huang1, Binbin Tang2, Bocheng Liang2, Yingdelong Mao2, Jianyou Li3, Xiaolin Shi2, Kang Liu2
  • 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
  • 2Department of Osteology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
  • 3Department of Orthopedics, Huzhou Central Hospital, Huzhou, China
* Equal contribution
Received: July 1, 2021Accepted: November 22, 2021Published: January 24, 2022
https://doi.org/10.18632/aging.203848

Copyright: © 2022 Yuan 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 systemic bone disease characterized by decreased bone mass and deterioration of bone microstructure, which leads to increased bone fragility and increased risk of fractures. Casein kinase 2 interacting protein 1 (CKIP-1, also known as PLEKHO1) is involved in the biological process of bone formation, differentiation and apoptosis, and is a negative regulator of bone formation. QiangGuYin (QGY) is a famous TCM formula that has been widely used in China for the clinical treatment of postmenopausal osteoporosis for decades, but the effect in regulating CKIP-1 on osteoporosis is not fully understood. This study aimed to explore the potential mechanism of CKIP-1 participating in autophagy in bone cells through the AKT/mTOR signaling pathway and the regulatory effect of QGY. The results in vivo showed that QGY treatment can significantly improve the bone quality of osteoporotic rats, down-regulate the expression of CKIP-1, LC3II/I and RANKL, and up-regulated the expression of p62, p-AKT/AKT, p-mTOR/mTOR, RUNX2 and OPG. It is worth noting that the results in vitro confirmed that CKIP-1 interacts with AKT. By up-regulating the expression of Atg5 and down-regulating the p62, the level of LC3 (autophagosome) is increased, and the cells osteogenesis and differentiation are inhibited. QGY inhibits the combination of CKIP-1 and AKT in osteoblasts, activates the AKT/mTOR signaling pathway, inhibits autophagy, and promotes cell differentiation, thereby exerting an anti-osteoporosis effect. Therefore, QGY targeting CKIP-1 to regulate the AKT/mTOR-autophagy signaling pathway may represent a promising drug candidate for the treatment of osteoporosis.