Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration
dc.contributor.author | Lin, Chujiao | |
dc.contributor.author | Yang, Qiyuan | |
dc.contributor.author | Guo, Dongsheng | |
dc.contributor.author | Xie, Jun | |
dc.contributor.author | Yang, Yeon-Suk | |
dc.contributor.author | Chaugule, Sachin | |
dc.contributor.author | DeSouza, Ngoc | |
dc.contributor.author | Oh, Won-Taek | |
dc.contributor.author | Li, Rui | |
dc.contributor.author | Chen, Zhihao | |
dc.contributor.author | John, Aijaz A | |
dc.contributor.author | Qiu, Qiang | |
dc.contributor.author | Zhu, Lihua Julie | |
dc.contributor.author | Greenblatt, Matthew B | |
dc.contributor.author | Ghosh, Sankar | |
dc.contributor.author | Li, Shaoguang | |
dc.contributor.author | Gao, Guangping | |
dc.contributor.author | Haynes, Cole | |
dc.contributor.author | Emerson, Charles P. Jr. | |
dc.contributor.author | Shim, Jae-Hyuck | |
dc.date.accessioned | 2022-12-22T15:20:36Z | |
dc.date.available | 2022-12-22T15:20:36Z | |
dc.date.issued | 2022-11-11 | |
dc.identifier.citation | Lin 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.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-022-34694-8 | en_US |
dc.identifier.pmid | 36369293 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/51491 | |
dc.description.abstract | Although 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.iso | en | en_US |
dc.relation.ispartof | Nature Communications | en_US |
dc.relation.url | https://doi.org/10.1038/s41467-022-34694-8 | en_US |
dc.rights | 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/. | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Bone development | en_US |
dc.subject | Drug delivery | en_US |
dc.title | Impaired mitochondrial oxidative metabolism in skeletal progenitor cells leads to musculoskeletal disintegration | en_US |
dc.type | Journal Article | en_US |
dc.source.journaltitle | Nature communications | |
dc.source.volume | 13 | |
dc.source.issue | 1 | |
dc.source.beginpage | 6869 | |
dc.source.endpage | ||
dc.source.country | England | |
dc.identifier.journal | Nature communications | |
refterms.dateFOA | 2022-12-22T15:20:37Z | |
dc.contributor.department | Horae Gene Therapy Center | en_US |
dc.contributor.department | Li Weibo Institute for Rare Diseases Research | en_US |
dc.contributor.department | Medicine | en_US |
dc.contributor.department | Microbiology and Physiological Systems | en_US |
dc.contributor.department | Molecular, Cell and Cancer Biology | en_US |
dc.contributor.department | Neurology | en_US |
dc.contributor.department | Wellstone Center for FSHD | en_US |