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Series GSE205732 Query DataSets for GSE205732
Status Public on Jun 09, 2023
Title Glucocorticoid-stimulated senescence phenotype in differentiated bone marrow adipocytes treated with PPARgamma inhibitor
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Glucocorticoids, powerful anti-inflammatory and immunosuppressive agents, can decrease bone mass and quality and increase bone marrow adiposity. Here, we show that a small number of bone marrow adipocytes (BMAds) in mice undergo rapid cellular senescence in response to glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype (SASP), which reinforces and spreads senescence in the bone/bone marrow microenvironment in a paracrine manner. Mechanistically, glucocorticoid treatment increases the synthesis of oxylipins such as 15d-PGJ2 in BMAds to positively regulate the activity of PPARĪ³, which stimulates the expression of key cellular senescence effector genes. PPARĪ³ activation, in turn, promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Inhibition of the initial BMAd senescence by deleting p16INK4a from adipocytes or pharmacological suppression of the SASP efficiently interrupts the secondary spread of senescent cells and alleviates glucocorticoid-induced bone deficits. We identify senescent BMAds as initial mediators for glucocorticoid-induced bone deterioration and reveal a lipid metabolism circuit that robustly triggers the senescence of BMAds.
Overall design In vitro stimulation of differentiated bone marrow adipocytes with or without glucocorticoid and /or PPARgamma inhibitor GW9662.
Contributor(s) Wan M, Cao X, Liu X
Citation(s) 37019080
Submission date Jun 08, 2022
Last update date Jun 09, 2023
Contact name Mei Wan
Phone 2054470577
Organization name Johns Hopkins Hospital
Department Department of Orthopedics
Lab Mei Wan
Street address 720 Rutland Ave,Ross research buil
City baltimore
State/province Maryland
ZIP/Postal code 21205
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (8)
GSM6222382 BMAd cells, Control1 [C1]
GSM6222383 BMAd cells, Control2 [C3]
GSM6222384 BMAd cells, GC1 [G1]
BioProject PRJNA847251

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Supplementary file Size Download File type/resource
GSE205732_TPM_values.txt.gz 4.1 Mb (ftp)(http) TXT
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