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Glucocorticoid-stimulated senescence phenotype in differentiated bone marrow adipocytes treated with PPARgamma inhibitor

ABSTRACT: 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 PPARγ, which stimulates the expression of key cellular senescence effector genes. PPARγ 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE205732 | GEO | 2023/06/09

REPOSITORIES: GEO

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MLL1 is essential for the senescence-associated secretory phenotype [RNA-Seq]

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2016-02-23 | E-GEOD-78138 | biostudies-arrayexpress

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