Advanced science (Weinheim, Baden-Wurttemberg, Germany)Jul 13, 2026

Parkin reduces cell damage and bone loss caused by steroids by modifying a fat-processing protein

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 14, 2026

Abstract

Long-term glucocorticoid use may induce typical ferroptosis in bone marrow mesenchymal stem cells.

Parkin expression is significantly downregulated in glucocorticoid-induced osteoporosis (GIOP) models.
Knocking down Parkin worsens lipid peroxidation, iron accumulation, and mitochondrial dysfunction, while inhibiting bone formation and promoting fat cell formation.
Overexpressing Parkin can reverse the negative effects seen with its knockdown.
Parkin binds to ACSL4, leading to its degradation through a specific cellular process.
Bone-targeted lipid nanoparticles carrying mRNA successfully inhibited ferroptosis and restored bone cell differentiation in laboratory settings.
In a mouse model of GIOP, these nanoparticles improved bone microstructure and altered gene expression related to ferroptosis and fat metabolism.

Simplified

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 polyubiquitination and proteasomal degradation. Based on these findings, we constructed DSS6-modified bone-targeted lipid nanoparticles (LNPs) (Parkin-LNP@DSS6), which efficiently encapsulated mRNA and exhibited excellent bone-homing ability. Parkin-LNP@DSS6 inhibited ferroptosis and restored osteogenic differentiation in vitro, and significantly improved bone microstructural parameters in GIOP mice. Transcriptome sequencing confirmed suppression of ferroptosis and fatty acid metabolism pathways. Collectively, this study reveals a novel mechanism by which Parkin inhibits BMSCs ferroptosis via K48 ubiquitination-mediated degradation of ACSL4 to alleviate GIOP, and provides a promising bone-targeted mRNA delivery strategy for GIOP and other ferroptosis-related bone diseases.

Full Text

Full text is available at the source.

View Full Text ↗

Parkin reduces cell damage and bone loss caused by steroids by modifying a fat-processing protein

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief