ArticleJournal of orthopaedic surgery and research2025
Icariin promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by activating PI3K-AKT-UTX/EZH2 signaling in steroid-induced femoral head osteonecrosis.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- 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
- HIRA promotes osteogenic differentiation of BMSCs and ameliorates osteoporosis by mediating M2 polarization of macrophages through the YAP1/β-catenin pathway.Molecular and cellular biochemistry · 2026Article
- Hydroxysafflor yellow A attenuatesovariectomy induced bone loss andpromotes osteogenesis via PI3K/AKT activation in an in vitro BMSC model.Scientific reports · 2026Article
- Dexras1 plays a crucial role in glucocorticoid-induced osteonecrosis of the femoral head by mediating imbalance between osteogenesis and adipogenesis.Cellular and molecular life sciences : CMLS · 2026Article
- Icariin as a Metabolic Regulator of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Therapeutic Implications to Bone Homeostasis.Journal of inflammation research · 2026Review
- Identification and validation of biomarkers of Shenggu Zaizao Wan in the treatment of steroid-induced osteonecrosis of the femoral head by integrating network pharmacology and bulk transcriptomic.Frontiers in medicine · 2026Article
- Icariin improves metabolic response to exercise by promoting TFEB-dependent mitochondrial clearance and metabolic reprogramming in C57BL/6 mice and C2C12 myotubes.Frontiers in nutrition · 2026Article
- The role of post-translational modifications in osteonecrosis of the femoral head.Frontiers in cell and developmental biology · 2026Review
- Emerging Strategies for Bioactive Agent-Loaded Xenogeneic Bone Scaffolds in Regenerative Medicine: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Osteogenic action of the natural plant material icariin and its potential use in biomedical tissue engineering.American journal of translational research · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
backgroundDifferentiation of bone marrow mesenchymal stem cells (BMSCs) is pivotal in the pathogenesis of steroid-induced femoral head osteonecrosis. Icariin, an active ingredient in Epimedii herba, has the potential to regulate osteogenic differentiation of BMSCs. Nevertheless, the related mechanism is still unclear. The study aimed to explore whether icariin can affect osteogenic differentiation by activating PI3K/AKT signaling to alter UTX and EZH2 expression and thus regulating osteogenesis-related genes in BMSCs.
methodsBMSCs were collected from Sprague Dawley rats and identified by measuring the positive ratios of cell markers using flow cytometry. Cells were treated with 1 μmol/L dexamethasone (DEX) for 24 h with or without 0.1-10 μM of icariin treatment. Cell counting Kit-8 (CCK-8) assays and flow cytometry analyses were performed to measure cell viability and apoptosis. Western blotting was conducted for measurement of apoptotic markers, factors involved in the PI3K/AKT-UTX/EZH2 pathway, osteogenic markers, and adipogenesis-related factors. Alizarin red S staining and Oil-red O staining were performed to measure the effect of DEX, icariin, UTX overexpression, or EZH2 knockdown on osteogenic and adipogenic differentiation of BMSCs.
resultsIcariin ameliorated DEX-induced rat BMSC injury. Icariin activated the PI3K/AKT signaling, thereby upregulating UTX and phosphorylated EZH2 levels while inhibiting EZH2 and H3K27me3 expression. Additionally, icariin promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs. Importantly, overexpressing UTX or silencing EZH2 exerted similar effects on BMSC differentiation as icariin did.
conclusionsIcariin promotes osteogenic differentiation of DEX-treated BMSCs by activating PI3K/AKT signaling to upregulate UTX and inhibit EZH2, finally inducing H3K27me3 depletion.
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