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Title: Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

Abstract

Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.

Authors:
 [1];  [2];  [3];  [4];  [5];  [1];  [1];  [1];  [1];  [1];
  1. State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an 710032 (China)
  2. (China)
  3. Department of Gynecology of Shaanxi Provincial People’s Hospital, Xi’an, 710068 (China)
  4. Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China)
  5. Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi’an 710032 (China)
Publication Date:
OSTI Identifier:
22598794
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 476; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABSORPTION SPECTROSCOPY; COMPUTERIZED TOMOGRAPHY; CONNECTIVE TISSUE CELLS; GENES; IN VIVO; INHIBITION; LIGANDS; MICE; MITOCHONDRIA; OSTEOPOROSIS; OVARIES; PEPTIDES; RECEPTORS; SKELETON

Citation Formats

Ming, Wei, E-mail: weiming@xiyi.edu.cn, Department of Pharmacology, Xi’an Medical University, Xi’an 710021, Lu, Gan, E-mail: leonming99@163.com, Xin, Sha, E-mail: 248967979@qq.com, Huanyu, Lu, E-mail: 2366927258@qq.com, Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn, Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn, Chengming, Xu, E-mail: chengmingxu@yeah.net, Banjun, Ruan, E-mail: running@163.com, Li, Wang, E-mail: wanglifw@fmmu.edu.cn, and and others. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.135.
Ming, Wei, E-mail: weiming@xiyi.edu.cn, Department of Pharmacology, Xi’an Medical University, Xi’an 710021, Lu, Gan, E-mail: leonming99@163.com, Xin, Sha, E-mail: 248967979@qq.com, Huanyu, Lu, E-mail: 2366927258@qq.com, Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn, Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn, Chengming, Xu, E-mail: chengmingxu@yeah.net, Banjun, Ruan, E-mail: running@163.com, Li, Wang, E-mail: wanglifw@fmmu.edu.cn, & and others. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. United States. doi:10.1016/J.BBRC.2016.05.135.
Ming, Wei, E-mail: weiming@xiyi.edu.cn, Department of Pharmacology, Xi’an Medical University, Xi’an 710021, Lu, Gan, E-mail: leonming99@163.com, Xin, Sha, E-mail: 248967979@qq.com, Huanyu, Lu, E-mail: 2366927258@qq.com, Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn, Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn, Chengming, Xu, E-mail: chengmingxu@yeah.net, Banjun, Ruan, E-mail: running@163.com, Li, Wang, E-mail: wanglifw@fmmu.edu.cn, and and others. Fri . "Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation". United States. doi:10.1016/J.BBRC.2016.05.135.
@article{osti_22598794,
title = {Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation},
author = {Ming, Wei, E-mail: weiming@xiyi.edu.cn and Department of Pharmacology, Xi’an Medical University, Xi’an 710021 and Lu, Gan, E-mail: leonming99@163.com and Xin, Sha, E-mail: 248967979@qq.com and Huanyu, Lu, E-mail: 2366927258@qq.com and Yinghao, Jiang, E-mail: jiangyh@fmmu.edu.cn and Xiaoying, Lei, E-mail: leixiaoy@fmmu.edu.cn and Chengming, Xu, E-mail: chengmingxu@yeah.net and Banjun, Ruan, E-mail: running@163.com and Li, Wang, E-mail: wanglifw@fmmu.edu.cn and and others},
abstractNote = {Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.},
doi = {10.1016/J.BBRC.2016.05.135},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 476,
place = {United States},
year = {Fri Aug 05 00:00:00 EDT 2016},
month = {Fri Aug 05 00:00:00 EDT 2016}
}