| First Author | Liu X | Year | 2023 |
| Journal | Cell Metab | Volume | 35 |
| Issue | 4 | Pages | 667-684.e6 |
| PubMed ID | 37019080 | Mgi Jnum | J:346266 |
| Mgi Id | MGI:7463795 | Doi | 10.1016/j.cmet.2023.03.005 |
| Citation | Liu X, et al. (2023) Oxylipin-PPARgamma-initiated adipocyte senescence propagates secondary senescence in the bone marrow. Cell Metab 35(4):667-684.e6 |
| abstractText | The chronic use of glucocorticoids decreases bone mass and quality and increases bone-marrow adiposity, but the underlying mechanisms remain unclear. Here, we show that bone-marrow adipocyte (BMAd) lineage cells in adult mice undergo rapid cellular senescence upon glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype, which spreads senescence in bone and bone marrow. Mechanistically, glucocorticoids increase the synthesis of oxylipins, such as 15d-PGJ2, for peroxisome proliferator-activated receptor gamma (PPARgamma) activation. PPARgamma stimulates the expression of key senescence genes and also promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Transplanting senescent BMAds into the bone marrow of healthy mice is sufficient to induce the secondary spread of senescent cells and bone-loss phenotypes, whereas transplanting BMAds harboring a p16INK4a deletion did not show such effects. Thus, glucocorticoid treatment induces a lipid metabolic circuit that robustly triggers the senescence of BMAd lineage cells that, in turn, act as the mediators of glucocorticoid-induced bone deterioration. |
