2. Academic Validation
  3. Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway

Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway

  • Free Radic Biol Med. 2021 Feb 1;163:356-368. doi: 10.1016/j.freeradbiomed.2020.12.235.
Liang Chen 1,  Xiang Shi 2,  Jun Xie 1,  She-Ji Weng 3,  Zhong-Jie Xie 3,  Jia-Hao Tang 1,  De-Yi Yan 1,  Bing-Zhang Wang 1,  Kang-Hao Fang 1,  Chen-Xuan Hong 1,  Zong-Yi Wu 3,  Lei Yang 4
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China.
  • 2 Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 4 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China. Electronic address: [email protected].
PMID: 33385540 DOI: 10.1016/j.freeradbiomed.2020.12.235
Abstract

Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects Mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated Mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-α phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated Mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.

Keywords

AMPK; Apelin; Mitophagy; Osteoporosis; Oxidative stress.

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