Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Publication

Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Immunity | 2017

Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis. E2F1 targets included glycolysis and metabolic genes including CKB that enabled cells to meet metabolic demands in challenging environments, as well as inflammatory cytokine-driven target genes. Expression quantitative trait locus analysis linked increased COMMD1 expression with decreased bone erosion in rheumatoid arthritis. Myeloid deletion of Commd1 resulted in increased osteoclastogenesis in arthritis and inflammatory osteolysis models. These results identify COMMD1 and an E2F-metabolic pathway as key regulators of osteoclastogenic responses under pathological inflammatory conditions and provide a mechanism by which hypoxia augments inflammation and bone destruction.

Pubmed ID: 28723554 RIS Download

Research resources used in this publication

None found

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

Agency: NIAMS NIH HHS, United States
Id: R00 AR061430
Agency: NIDCR NIH HHS, United States
Id: R01 DE019420
Agency: NIAMS NIH HHS, United States
Id: R01 AR069562
Agency: NIAMS NIH HHS, United States
Id: R01 AR050401
Agency: NIAID NIH HHS, United States
Id: R01 AI044938

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

Cuffdiff (tool)

RRID:SCR_001647

Software that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.

View all literature mentions

TopHat (tool)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

View all literature mentions