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.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China; Department of Pharmacology, Xi'an Medical University, Xi'an 710021, PR China. Electronic address: weiming@xiyi.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Ming
authors.affiliation: Department of Gynecology of Shaanxi Provincial People's Hospital, Xi'an, 710068, PR China. Electronic address: leonming99@163.com.
authors.forename: Gan
authors.initials: G
authors.lastname: Lu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: 248967979@qq.com.
authors.forename: Sha
authors.initials: S
authors.lastname: Xin
authors.affiliation: 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, PR China. Electronic address: 2366927258@qq.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Huanyu
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: jiangyh@fmmu.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yinghao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: leixiaoy@fmmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiaoying
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: chengmingxu@yeah.net.
authors.forename: Xu
authors.initials: X
authors.lastname: Chengming
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: running@163.com.
authors.forename: Ruan
authors.initials: R
authors.lastname: Banjun
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: wanglifw@fmmu.edu.cn.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: luzfliuq@fmmu.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Zifan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy / Q000009:adverse effects*; D010455:Peptides / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: C000619256:MOTS-c peptide, human; D024101:Mitochondrial Proteins; D010455:Peptides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPK; MOTS-c; Osteoblast; Osteoclast; Osteoporosis