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| 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
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| 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.
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| Overall design |
In vitro stimulation of differentiated bone marrow adipocytes with or without glucocorticoid and /or PPARgamma inhibitor GW9662.
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| Contributor(s) |
Wan M, Cao X, Liu X |
| Citation(s) |
37019080 |
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| Submission date |
Jun 08, 2022 |
| Last update date |
Jun 09, 2023 |
| Contact name |
Mei Wan |
| E-mail(s) |
mwan4@jhmi.edu
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| Phone |
2054470577
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| Organization name |
Johns Hopkins Hospital
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| Department |
Department of Orthopedics
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| Lab |
Mei Wan
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| Street address |
720 Rutland Ave,Ross research buil
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| City |
baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA847251 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205732_TPM_values.txt.gz |
4.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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