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dc.contributor.authorLin, Chujiao
dc.contributor.authorYang, Qiyuan
dc.contributor.authorGuo, Dongsheng
dc.contributor.authorXie, Jun
dc.contributor.authorYang, Yeon-Suk
dc.contributor.authorChaugule, Sachin
dc.contributor.authorDeSouza, Ngoc
dc.contributor.authorOh, Won-Taek
dc.contributor.authorLi, Rui
dc.contributor.authorChen, Zhihao
dc.contributor.authorJohn, Aijaz A
dc.contributor.authorQiu, Qiang
dc.contributor.authorZhu, Lihua Julie
dc.contributor.authorGreenblatt, Matthew B
dc.contributor.authorGhosh, Sankar
dc.contributor.authorLi, Shaoguang
dc.contributor.authorGao, Guangping
dc.contributor.authorHaynes, Cole
dc.contributor.authorEmerson, Charles P. Jr.
dc.contributor.authorShim, Jae-Hyuck
dc.date.accessioned2022-12-22T15:20:36Z
dc.date.available2022-12-22T15:20:36Z
dc.date.issued2022-11-11
dc.identifier.citationLin C, Yang Q, Guo D, Xie J, Yang YS, Chaugule S, DeSouza N, Oh WT, Li R, Chen Z, John AA, Qiu Q, Zhu LJ, Greenblatt MB, Ghosh S, Li S, Gao G, Haynes C, Emerson CP, Shim JH. Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration. Nat Commun. 2022 Nov 11;13(1):6869. doi: 10.1038/s41467-022-34694-8. PMID: 36369293; PMCID: PMC9652319.en_US
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-022-34694-8en_US
dc.identifier.pmid36369293
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51491
dc.description.abstractAlthough skeletal progenitors provide a reservoir for bone-forming osteoblasts, the major energy source for their osteogenesis remains unclear. Here, we demonstrate a requirement for mitochondrial oxidative phosphorylation in the osteogenic commitment and differentiation of skeletal progenitors. Deletion of Evolutionarily Conserved Signaling Intermediate in Toll pathways (ECSIT) in skeletal progenitors hinders bone formation and regeneration, resulting in skeletal deformity, defects in the bone marrow niche and spontaneous fractures followed by persistent nonunion. Upon skeletal fracture, Ecsit-deficient skeletal progenitors migrate to adjacent skeletal muscle causing muscle atrophy. These phenotypes are intrinsic to ECSIT function in skeletal progenitors, as little skeletal abnormalities were observed in mice lacking Ecsit in committed osteoprogenitors or mature osteoblasts. Mechanistically, Ecsit deletion in skeletal progenitors impairs mitochondrial complex assembly and mitochondrial oxidative phosphorylation and elevates glycolysis. ECSIT-associated skeletal phenotypes were reversed by in vivo reconstitution with wild-type ECSIT expression, but not a mutant displaying defective mitochondrial localization. Collectively, these findings identify mitochondrial oxidative phosphorylation as the prominent energy-driving force for osteogenesis of skeletal progenitors, governing musculoskeletal integrity.en_US
dc.language.isoenen_US
dc.relation.ispartofNature Communicationsen_US
dc.relation.urlhttps://doi.org/10.1038/s41467-022-34694-8en_US
dc.rightsCopyright © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectBone developmenten_US
dc.subjectDrug deliveryen_US
dc.titleImpaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegrationen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNature communications
dc.source.volume13
dc.source.issue1
dc.source.beginpage6869
dc.source.endpage
dc.source.countryEngland
dc.identifier.journalNature communications
refterms.dateFOA2022-12-22T15:20:37Z
dc.contributor.departmentHorae Gene Therapy Centeren_US
dc.contributor.departmentLi Weibo Institute for Rare Diseases Researchen_US
dc.contributor.departmentMedicineen_US
dc.contributor.departmentMicrobiology and Physiological Systemsen_US
dc.contributor.departmentMolecular, Cell and Cancer Biologyen_US
dc.contributor.departmentNeurologyen_US
dc.contributor.departmentWellstone Center for FSHDen_US


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Copyright © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.