Ubiquitination of ACSL4 by Parkin Suppresses Ferroptosis and Rescues Glucocorticoid-Induced Bone Loss.

ABSTRACT: Long-term glucocorticoids (GCs) use induces glucocorticoids-induced osteoporosis (GIOP), but the underlying mechanisms remain unclear. This study investigated the role of Parkin in regulating ACSL4-mediated ferroptosis in GIOP and developed a bone-targeted mRNA therapeutic strategy. Using dexamethasone (DEX)-treated bone marrow mesenchymal stem cells (BMSCs) and a GIOP mouse model, we found that GCs induced typical ferroptosis in BMSCs. Parkin expression was significantly downregulated in GIOP models. Parkin knockdown exacerbated DEX-induced lipid peroxidation, iron accumulation, and mitochondrial dysfunction, while inhibiting osteogenesis and promoting adipogenesis; Parkin overexpression reversed these phenotypes. Mechanistically, Parkin directly bound to ACSL4 and promoted its K48-linked

SUBMITTER: Han LJ 

PROVIDER: S-EPMC13359397 | biostudies-literature | 2026 Oct

REPOSITORIES: biostudies-literature