MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRα

The Journal of Clinical Investigation
Seyeon BaeKyung-Hyun Park-Min

Abstract

Osteoporosis is a metabolic bone disorder associated with compromised bone strength and an increased risk of fracture. Inhibition of the differentiation of bone-resorbing osteoclasts is an effective strategy for the treatment of osteoporosis. Prior work by our laboratory and others has shown that MYC promotes osteoclastogenesis in vitro, but the underlying mechanisms are not well understood. In addition, the in vivo importance of osteoclast-expressed MYC in physiological and pathological bone loss is not known. Here, we have demonstrated that deletion of Myc in osteoclasts increases bone mass and protects mice from ovariectomy-induced (OVX-induced) osteoporosis. Transcriptomic analysis revealed that MYC drives metabolic reprogramming during osteoclast differentiation and functions as a metabolic switch to an oxidative state. We identified a role for MYC action in the transcriptional induction of estrogen receptor-related receptor α (ERRα), a nuclear receptor that cooperates with the transcription factor nuclear factor of activated T cells, c1 (NFATc1) to drive osteoclastogenesis. Accordingly, pharmacological inhibition of ERRα attenuated OVX-induced bone loss in mice. Our findings highlight a MYC/ERRα pathway that contributes t...Continue Reading

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Citations

May 23, 2017·The Journal of Clinical Investigation·Joseph Lorenzo
Jun 8, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Yuyu LiXu Feng
Sep 12, 2019·Seminars in Immunopathology·Dengbao Yang, Yihong Wan
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Sep 12, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Klemens VertesichXu Yang
Apr 20, 2018·Cellular and Molecular Life Sciences : CMLS·Kyung-Hyun Park-Min
Sep 26, 2019·Seminars in Immunopathology·Kyung-Hyun Park-Min
Jan 13, 2021·Cells·Haemin KimKyung-Hyun Park-Min
Jan 12, 2021·Bone Research·Takayuki FujiiLionel B Ivashkiv
Feb 11, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Se Hwan MunKyung-Hyun Park-Min
Mar 1, 2021·Journal of Periodontal Research·Natalie Aparecida Rodrigues FernandesMorgana Rodrigues Guimarães-Stabili
Feb 19, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Moritz WeiglMatthias Hackl
Sep 6, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Danqi YaoXiao Zhu
Apr 20, 2021·Frontiers in Immunology·Yao YaoMeng Zhang
May 25, 2021·Frontiers in Molecular Biosciences·Ming-Li ZouFeng-Lai Yuan
Oct 22, 2021·Human Molecular Genetics·Jonathan GreenbaumHong-Wen Deng

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Datasets Mentioned

BETA
SRP096890

Methods Mentioned

BETA
Assay
Transfection
PCR
RNA-seq

Software Mentioned

GraphPad
OsteoMetrics
OsteoMeasure
GSEA
R
TopHat
Cufflinks
Ingenuity Pathway Analysis ( IPA )
GraphPad Prism

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