2. Academic Validation
  3. Apelin-13 treats postmenopausal osteoporosis by reducing mitochondrial oxidative phosphorylation and modulating the OPG/RANK/RANKL/IGF-1 pathway

Apelin-13 treats postmenopausal osteoporosis by reducing mitochondrial oxidative phosphorylation and modulating the OPG/RANK/RANKL/IGF-1 pathway

  • Biochem Biophys Res Commun. 2025 Sep 29:786:152738. doi: 10.1016/j.bbrc.2025.152738.
XiaoRong Meng 1,  Dandan Meng 2,  Chenhui Xiang 3,  Lingling Pu 4,  Xiaofei Yin 5,  Jing Yang 6
Affiliations

Affiliations

  • 1 Department of Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, Sichuan, China. Electronic address: doctorMengxr@outlook.com.
  • 2 Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, Sichuan, China. Electronic address: 18980133792@163.com.
  • 3 Department of Urology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China. Electronic address: xiangch6617@my.com.
  • 4 Experimental Teaching Center of Biotechnology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China; Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases at Chengdu Medical College of Sichuan Province, Chengdu, 610500, China; Irradiation Preservation and Effect Key Laboratory of Sichuan Province, Chengdu, 610500, China. Electronic address: pulingling426@cmc.edu.cn.
  • 5 Experimental Teaching Center of Biotechnology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China; Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases at Chengdu Medical College of Sichuan Province, Chengdu, 610500, China; Irradiation Preservation and Effect Key Laboratory of Sichuan Province, Chengdu, 610500, China. Electronic address: 18190871235@163.com.
  • 6 Experimental Teaching Center of Biotechnology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China; Key Laboratory of Target Discovery and Protein Drug Development in Major Diseases at Chengdu Medical College of Sichuan Province, Chengdu, 610500, China; Irradiation Preservation and Effect Key Laboratory of Sichuan Province, Chengdu, 610500, China. Electronic address: jingyang@cmc.edu.cn.
PMID: 41043277 DOI: 10.1016/j.bbrc.2025.152738
Abstract

Objective: Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP.

Methods: A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques-including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA-were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects.

Results: Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed Apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased Alkaline Phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of Reactive Oxygen Species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355.

Conclusion: Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial Oxidative Phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.

Keywords

Apelin-13; Mitochondrial oxidative phosphorylation; OPG/RANK/RANKL/IGF-1 signaling pathway; PMOP.

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