PGC1β Organizes the Osteoclast Cytoskeleton by Mitochondrial Biogenesis and Activation
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- Yan Zhang
- Center for Translational MedicineThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShanxiPeople's Republic of China
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- Nidhi Rohatgi
- Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisMOUSA
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- Deborah J Veis
- Department of Medicine, Division of Bone and Mineral DiseasesWashington University School of MedicineSt. LouisMOUSA
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- Joel Schilling
- Department of Medicine, Division of CardiologyWashington University School of MedicineSt. LouisMOUSA
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- Steven L Teitelbaum
- Department of Medicine, Division of Bone and Mineral DiseasesWashington University School of MedicineSt. LouisMOUSA
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- Wei Zou
- Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisMOUSA
抄録
<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title> </jats:title> <jats:p>Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type. Mitochondrial biogenesis and function are diminished in PGC1βLysM osteoclasts. All abnormalities are normalized by PGC1β transduction. Furthermore, OXPHOS inhibitors reproduce the phenotype of PGC1β deletion. PGC1β's organization of the osteoclast cytoskeleton is mediated by expression of GIT1, which also promotes mitochondrial biogenesis. Thus, osteoclast mitochondria regulate the cell's resorptive activity by promoting cytoskeletal organization. © 2018 American Society for Bone and Mineral Research.</jats:p> </jats:sec>
収録刊行物
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- Journal of Bone and Mineral Research
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Journal of Bone and Mineral Research 33 (6), 1114-1125, 2018-03-08
Oxford University Press (OUP)