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Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis
by
Zhu, Haoran
, Li, Hu
, Chen, Hongxing
, Wen, Moshan
, Lu, Hongduo
, Fan, Yinuo
, Gao, Shihua
, Yang, Deqiang
in
1-Phosphatidylinositol 3-kinase
/ 631/337
/ 692/420
/ 740Y-P
/ Agonists
/ AKT protein
/ Animals
/ Bioinformatics
/ Bone diseases
/ Cbfa-1 protein
/ Cell death
/ Cell Line
/ Copper
/ Copper - metabolism
/ Cuproptosis
/ Dexamethasone
/ Dexamethasone - adverse effects
/ Disease Models, Animal
/ Drug dosages
/ Experiments
/ Female
/ Femur
/ Femur Head - drug effects
/ Femur Head - metabolism
/ Femur Head - pathology
/ Femur Head Necrosis - chemically induced
/ Femur Head Necrosis - metabolism
/ Femur Head Necrosis - pathology
/ Femur Head Necrosis - prevention & control
/ Genes
/ Glucocorticoids - adverse effects
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Male
/ Medical research
/ Mice
/ multidisciplinary
/ Necrosis
/ Osteogenesis - drug effects
/ Osteonecrosis
/ Phosphatidylinositol 3-Kinases - metabolism
/ PI3K/AKT signaling pathway
/ Proteins
/ Proteomics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Sprague-Dawley
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signal Transduction - drug effects
/ Steroid-induced osteonecrosis of the femoral head
/ Steroids
/ Steroids - adverse effects
/ Traditional Chinese medicine
2025
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Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis
by
Zhu, Haoran
, Li, Hu
, Chen, Hongxing
, Wen, Moshan
, Lu, Hongduo
, Fan, Yinuo
, Gao, Shihua
, Yang, Deqiang
in
1-Phosphatidylinositol 3-kinase
/ 631/337
/ 692/420
/ 740Y-P
/ Agonists
/ AKT protein
/ Animals
/ Bioinformatics
/ Bone diseases
/ Cbfa-1 protein
/ Cell death
/ Cell Line
/ Copper
/ Copper - metabolism
/ Cuproptosis
/ Dexamethasone
/ Dexamethasone - adverse effects
/ Disease Models, Animal
/ Drug dosages
/ Experiments
/ Female
/ Femur
/ Femur Head - drug effects
/ Femur Head - metabolism
/ Femur Head - pathology
/ Femur Head Necrosis - chemically induced
/ Femur Head Necrosis - metabolism
/ Femur Head Necrosis - pathology
/ Femur Head Necrosis - prevention & control
/ Genes
/ Glucocorticoids - adverse effects
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Male
/ Medical research
/ Mice
/ multidisciplinary
/ Necrosis
/ Osteogenesis - drug effects
/ Osteonecrosis
/ Phosphatidylinositol 3-Kinases - metabolism
/ PI3K/AKT signaling pathway
/ Proteins
/ Proteomics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Sprague-Dawley
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signal Transduction - drug effects
/ Steroid-induced osteonecrosis of the femoral head
/ Steroids
/ Steroids - adverse effects
/ Traditional Chinese medicine
2025
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Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis
by
Zhu, Haoran
, Li, Hu
, Chen, Hongxing
, Wen, Moshan
, Lu, Hongduo
, Fan, Yinuo
, Gao, Shihua
, Yang, Deqiang
in
1-Phosphatidylinositol 3-kinase
/ 631/337
/ 692/420
/ 740Y-P
/ Agonists
/ AKT protein
/ Animals
/ Bioinformatics
/ Bone diseases
/ Cbfa-1 protein
/ Cell death
/ Cell Line
/ Copper
/ Copper - metabolism
/ Cuproptosis
/ Dexamethasone
/ Dexamethasone - adverse effects
/ Disease Models, Animal
/ Drug dosages
/ Experiments
/ Female
/ Femur
/ Femur Head - drug effects
/ Femur Head - metabolism
/ Femur Head - pathology
/ Femur Head Necrosis - chemically induced
/ Femur Head Necrosis - metabolism
/ Femur Head Necrosis - pathology
/ Femur Head Necrosis - prevention & control
/ Genes
/ Glucocorticoids - adverse effects
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Male
/ Medical research
/ Mice
/ multidisciplinary
/ Necrosis
/ Osteogenesis - drug effects
/ Osteonecrosis
/ Phosphatidylinositol 3-Kinases - metabolism
/ PI3K/AKT signaling pathway
/ Proteins
/ Proteomics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Sprague-Dawley
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signal Transduction - drug effects
/ Steroid-induced osteonecrosis of the femoral head
/ Steroids
/ Steroids - adverse effects
/ Traditional Chinese medicine
2025
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Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis
Journal Article
Activation of PI3K-AKT pathway prevents steroid-induced osteonecrosis of the femoral head via inhibiting Cuproptosis
2025
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Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
1-Phosphatidylinositol 3-kinase
/ 631/337
/ 692/420
/ 740Y-P
/ Agonists
/ Animals
/ Copper
/ Dexamethasone - adverse effects
/ Female
/ Femur
/ Femur Head Necrosis - chemically induced
/ Femur Head Necrosis - metabolism
/ Femur Head Necrosis - pathology
/ Femur Head Necrosis - prevention & control
/ Genes
/ Glucocorticoids - adverse effects
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Male
/ Mice
/ Necrosis
/ Phosphatidylinositol 3-Kinases - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Science
/ Signal Transduction - drug effects
/ Steroid-induced osteonecrosis of the femoral head
/ Steroids
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