ArticleScientific reports2025
Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Animal Models of Steroid-Induced Osteonecrosis of the Femoral Head Established by Different Doses of Lipopolysaccharide Combined with Glucocorticoids: A Systematic Review and Network Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- SLC25A12 mitigates mitochondrial dysfunction in myoblast senescence, and alleviates cuproptosis-related changes under copper stress.Biology direct · 2026Article
- Epigenetic dysregulation in osteonecrosis of the femoral head: a critical review of DNA methylation, histone modifications, and clinical translation.Journal of orthopaedic surgery and research · 2026Review
- Research advances of copper homeostasis and cuproptosis in orthopedic diseases.Cell death discovery · 2026Review
- Research Progress of Cuproptosis in Orthopaedics: Opportunities and Challenges.Journal of cellular and molecular medicine · 2026Review
- Jingangteng Capsule Attenuates Ulcerative Colitis via Maintaining the Homeostasis of Intestinal Microbiota and Metabolites, Inhibiting the PI3K-AKT-mTOR Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathway.Translational cancer research · 2026Article
- Cuproptosis: Biomarkers, Mechanisms and Treatments in Diseases.Molecules (Basel, Switzerland) · 2026Review
- Musculoskeletal disorders: does cuproptosis hold the key?Frontiers in cell and developmental biology · 2026Review
- Cuproptosis: A Potential Target for the Treatment of Systemic Lupus Erythematosus.Journal of inflammation research · 2026Review
- Down-regulation of THBS2 inhibits the malignant progression of Burkitt lymphoma by blocking the PI3K/AKT/c-MYC pathway.Frontiers in oncology · 2026Article
- Extracorporeal shock wave therapy alleviates glucocorticoid-induced injury and dysfunction of bone microvascular endothelial cells via the PI3K/AKT/FOXO1 pathway.Annals of joint · 2026Article
- Exploration of potential mechanisms and biomarkers related to ERS-associated RCD in steroid-induced osteonecrosis of the femoral head based on bioinformatics, with experimental validation.Frontiers in endocrinology · 2026Article
- SLC25A3 promotes hepatocellular carcinoma progression by inducing mitochondrial dysfunction and chromatin remodeling.Translational cancer research · 2025Article
- Systematic Comparison of Bone Proteome Extraction Methods to Allow for Integrated Proteomics-Metabolomics Correlation.Journal of proteome research · 2025Article
- PTGS2 Is Involved in Osteonecrosis of the Femoral Head and Bone Marrow Edema.International journal of genomics · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study delved into the role of the PI3K/AKT signaling pathway and cuproptosis in steroid-induced osteonecrosis of the femoral head (SIONFH), assessing the therapeutic potential of the PI3K agonist 740Y-P. We analyzed femoral head specimens from SIONFH patients using DIA proteomics, identifying differentially expressed proteins linked to cuproptosis. In vitro, MC3T3-E1 cells treated with dexamethasone (DEX) exhibited hallmarks of cuproptosis, including downregulation of DLAT, PDHB, SLC25A3, and FDX1, increased copper ions, and reduced osteogenic potential, as shown by decreased ALP activity and RUNX2/BMP2 expression. The PI3K/AKT pathway's modulation of FDX1 was key to cuproptosis regulation; activating it with 740Y-P restored FDX1 levels and partially recovered osteogenic capacity. An in vivo rat model of SIONFH treated with 740Y-P demonstrated improved bone parameters, reversed osteogenic suppression, and upregulated PI3K/AKT/FDX1 expression, validating the pathway's role in cuproptosis and the agonist's therapeutic potential for treating SIONFH and glucocorticoid-associated bone disorders.
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