Evidence map›Paper›PMID 42439361›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

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

Li-Jiang Han, Jian-Sen Miao, Yi-Feng Shi, Yi-Ting Tu, Yu-Zhe Lin, Lin-Jie Chen, Bing-Hao Lin, Hua-Lin Li, Xuan-Qi Zheng, Hong-Qiang Wu and 7 more

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Li-Jiang HanKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jian-Sen MiaoKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yi-Feng ShiKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0000-0003-1969-9352
Yi-Ting TuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yu-Zhe LinKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Lin-Jie ChenKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Bing-Hao LinKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hua-Lin LiKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Xuan-Qi ZhengKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hong-Qiang WuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Hai-Xiao LiuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Lei YangKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0009-0008-4079-5289
Ai-Min WuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0000-0002-8582-4599
Zhen LinKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jian XiaoKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0000-0001-7374-6506
Gang ZhengKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0009-0004-1663-4101
Chen JinKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID https://orcid.org/0009-0001-4332-4553

Funding

National Natural Science Foundation of China 82302826Natural Science Foundation of Zhejiang Province TGY24H060028Wenzhou Science and Technology Program Project ZY2023009
6 · The paper itself

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 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.

Indexed as

BMSCsbone‐targeted mRNA deliveryferroptosisglucocorticoids‐induced osteoporosisParkin/ACSL4

Identifiers

PMID42439361
PMCPMC13359397

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.