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Series GSE121793 Query DataSets for GSE121793
Status Public on Jan 31, 2019
Title Epigenetic regulation of NfatC1 transcription and osteoclastogenesis by nicotinamide phosphoribosyl transferase in the pathogenesis of arthritis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Nicotinamide phosphoribosyltransferase (NAMPT) functions in NAD synthesis, apoptosis, and inflammation. Dysregulation of NAMPT has been associated with several inflammatory diseases, including rheumatoid arthritis (RA). The purpose of this study was to investigate NAMPT’s role in arthritis using mouse and cellular models. Collagen-induced arthritis (CIA) in DBA/1J Nampt+/- mice was evaluated by ELISA, micro-CT and RNA-sequencing (RNA-seq). In vitro Nampt loss-of-function and gain-of-function studies on osteoclastogenesis were examined by TRAP staining, nascent RNA capture, luciferase reporter assays, and ChIP-PCR. Nampt-deficient mice presented with suppressed inflammatory bone destruction and disease progression in a CIA mouse model. Nampt expression was required for the epigenetic regulation of the Nfatc1 promoter and osteoclastogenesis. Finally, RNA-seq identified 690 differentially expressed genes in whole ankle joints which associated (P<0.05) with Nampt expression and CIA. Selected target was validated by RT-PCR or functional characterization. We have provided evidence that NAMPT functions as a genetic risk factor and a potential therapeutic target to RA.
 
Overall design Paired-end sequencing of RNA isolated from whole ankle joints of Nampt+/+ and Nampt+/- mice with and without CIA
 
Contributor(s) Li X, Islam S, Xiong M, Nsumu NN, Lee MW Jr, Zhang LQ, Ueki Y, Heruth DP, Lei GH, Ye SQ
Citation(s) 30774990
Submission date Oct 25, 2018
Last update date Feb 27, 2019
Contact name Daniel Paul Heruth
E-mail(s) dpheruth@cmh.edu
Phone 8169836502
Organization name Children's Mercy
Department Pediatrics
Street address 4th Floor PRC, 2401 Gillham Road
City Kansas City
State/province MO
ZIP/Postal code 64108
Country USA
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (8)
GSM3446251 sample_41
GSM3446252 sample_42
GSM3446253 sample_989
Relations
BioProject PRJNA498482
SRA SRP166867

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE121793_processed_data.txt.gz 805.6 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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