Evidence map›Paper›PMID 40444470›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

PSMD14 Stabilizes SLC7A11 to Ameliorate Glucocorticoid-Induced Osteoporosis by Suppressing Osteocyte Ferroptosis.

Yifeng Shi, Qian Tang, Sunren Sheng, Hongyi Jiang, Chen Jin, Chencheng Zhou, Chenglong Xie, Lin Zheng, Di Zhang, Hui Xu and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Sesamin Promotes Diabetic Wound Healing by Inhibiting Ferroptosis via the SIRT1/Keap1/Nrf2 Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Yifeng ShiKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Qian TangDepartment of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, 200233, China.
Sunren ShengKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Hongyi JiangKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
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, 325000, China.
Chencheng ZhouKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Chenglong XieKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Lin ZhengKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Di ZhangKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Hui XuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Cong XuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Haiwei MaDepartment of Orthopaedics Surgery, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.
Guangheng XiangKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Wenfei NiKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Xiaoyun PanKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, 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, 325000, China.
Huazi XuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Yu QianDepartment of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, China.
Aimin WuKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Xiangyang WangKey Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
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, 325000, China.ORCID https://orcid.org/0009-0004-1663-4101

Funding

National Natural Science Foundation of China 82302714Wenzhou Major Science and Technology Innovation Breakthrough ZY2024024Zhejiang Province Medical and Health Science and Technology Project 2024KY1283Zhejiang Provincial Natural Science Foundation of China LQ23H060003
6 · The paper itself

Abstract

Glucocorticoid-induced osteoporosis (GIOP) remains the most prevalent complication compromising bone health in patients undergoing glucocorticoid (GC) therapy. Despite its clinical significance, osteocyte death, a pivotal initiator of GC-driven bone metabolic imbalance, has received insufficient attention. This study identifies ferroptosis, an iron-dependent regulated cell death mechanism, as a novel pathological phenotype of osteocytes in GC microenvironments. Utilizing GPX4 conditional knockout mice and pharmacological ferroptosis inhibitors, this work demonstrates that osteocyte ferroptosis exacerbates GIOP progression. Metabolomic profiling reveals cystine insufficiency and glutathione depletion in GC-treated osteocytes. Mechanistically, GCs directly impede the deubiquitinase PSMD14 from binding to SLC7A11, thereby promoting SLC7A11 ubiquitination and proteasomal degradation, which sharply diminishes cystine uptake. Bone-targeting adeno-associated virus-mediated PSMD14 overexpression stabilized SLC7A11, attenuating both osteocytic ferroptosis and bone loss in GIOP mice. Through high-throughput virtual screening, this work identifies Pantethine as a potent PSMD14 activator that enhances deubiquitinase activity, restores SLC7A11 expression in osteocytes, and mitigates osteoporosis. Collectively, this study elucidates the role and mechanism of osteocyte ferroptosis in GIOP pathogenesis and proposes PSMD14-targeted therapy as a viable clinical strategy.

Indexed as

Amino Acid Transport System y+FerroptosisGlucocorticoidsOsteocytesOsteoporosisAnimalsHumansMiceMice, Inbred C57BLMice, KnockoutAmino Acid Transport System y+GlucocorticoidsSlc7a11 protein, mouseferroptosisglucocorticoid‐induced osteoporosisPSMD14SLC7A11ubiquitination

Identifiers

PMID40444470
PMCPMC12376700

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.