ArticlePeerJ2022
Glucocorticoids induce osteonecrosis of the femoral head in rats via PI3K/AKT/FOXO1 signaling pathway.
Article in PeerJ, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- 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
- 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
- Phosphatidylinositol-3-kinase/protein kinase B signaling dysregulation in steroid-induced osteonecrosis of the femoral head: A minireview of therapeutic implications.World journal of orthopedics · 2026Review
- 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
- 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
- Selenium Attenuates Dexamethasone-Induced Osteoblast Dysfunction and Prevents Femoral Head Osteonecrosis via PI3K/AKT/GSK3β Pathway Activation.Orthopaedic surgery · 2025Article
- The multifaceted roles of extracellular vesicles in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2025Review
- Exploring the Potential ofInternational journal of medical sciences · 2025Review
- Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head.Scientific reports · 2024Article
- TRIM21 silencing inhibits the apoptosis and expedites the osteogenic differentiation of dexamethasone‑induced MC3T3‑E1 cells by activating the Keap1/Nrf2 pathway.Experimental and therapeutic medicine · 2024Article
- Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.Orthopaedic surgery · 2024Article
- Article
- Identification and Validation of Potential Ferroptosis-Related Genes in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.Medicina (Kaunas, Lithuania) · 2023Article
- Experimental study of dexamethasone-loaded hollow hydroxyapatite microspheres applied to direct pulp capping of rat molars.Frontiers in endocrinology · 2023Article
- Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network.Toxins · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a disorder that causes severe disability in patients and has a high incidence worldwide. Although glucocorticoid (GC)-induced apoptosis of osteoblasts is an important cytological basis of SONFH, the detailed mechanism underlying SONFH pathogenesis remains elusive. PI3K/AKT signaling pathway was reported to involve in cell survival and apoptosis. Objective: We explored the role of PI3K/AKT/FOXO1 signaling pathway and its downstream targets during glucocorticoid -induced osteonecrosis of the femoral head. Methods: We obtained gene expression profile of osteoblasts subjected to dexamethasone (Dex) treatment from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out and functional enrichment analysis were conducted by bioinformatics analysis. Results: In Dex-treated osteoblasts, DEGs were mainly enriched in the FOXO signaling pathway. Dex inhibited MC3T3-E1 cell viability in a dose-dependent effect and induced apoptosis by increasing the expression levels of FOXO1, Bax, cleaved-Caspase-3, and cleaved-Caspase-9, while reducing the expression of Bcl-2. Notably, these results were reversed by siRNA-FOXO1 treatment. Dex inhibited PI3K/AKT signaling pathway, upregulated FOXO1 expression and increased FOXO1 nuclear translocation, which were reversed by IGF-1. Compared to normal rats, the femoral head of SONFH showed increased expression of FOXO1, increased number of apoptotic cells, and empty osteocytic lacunas, as well as decreased bone tissue content and femoral head integrity. Significantly, the effects of GC-induced SONFH were alleviated following IGF-1 treatment. Conclusion: Dex induces osteoblast apoptosis via the PI3K/AKT/FOXO1 signaling pathway. Our research offers new insights into the underlying molecular mechanisms of glucocorticoid-induced osteonecrosis in SONFH and proposes FOXO1 as a therapeutic target for this disease.
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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.