ArticleStem cell research & therapy2020
PTEN inhibitor VO-OHpic attenuates GC-associated endothelial progenitor cell dysfunction and osteonecrosis of the femoral head via activating Nrf2 signaling and inhibiting mitochondrial apoptosis pathway.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 48 citations in OpenAlex.
- Vascularized bone organoids: current advances and a biomimetic platform for osteonecrosis of the femoral head.Bone research · 2026Review
- ALDH5A1 as a key in osteonecrosis of the femoral head: Insights from bioinformatics and experimental validation.Biomedical reports · 2026Article
- Ergothioneine promotes osteogenesis and angiogenesis through PI3K/AKT pathway and prevents glucocorticoid-induced osteonecrosis of the femoral head.Scientific reports · 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
- Endoplasmic reticulum stress in steroid-induced osteonecrosis: translational bottlenecks and targeted therapeutic strategies.Frontiers in pharmacology · 2026Review
- Advances in Research on Autophagy in Steroid-Induced Osteonecrosis of the Femoral Head: Dual Regulation of Its Beneficial and Detrimental Effects.Drug design, development and therapy · 2026Review
- Exploring the pathogenesis of steroid-induced osteonecrosis of the femoral head co-regulated by mesenchymal stem cells and pyroptosis-related genes with the use of transcriptome.European journal of medical research · 2025Article
- Human Umbilical Cord Mesenchymal Stem Cells Prevent Steroid-Induced Avascular Necrosis of the Femoral Head by Modulating Cellular Autophagy.Biomedicines · 2024Article
- Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy.Biomedicines · 2024Review
- Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head.Bone research · 2024Article
- Mitochondrial maintenance as a novel target for treating steroid-induced osteonecrosis of femoral head: a narrative review.EFORT open reviews · 2024Review
- Fibroblast growth factor 23 inhibition attenuates steroid-induced osteonecrosis of the femoral head through pyroptosis.Scientific reports · 2024Article
- Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.Biomolecules · 2024Review
- MATN2 overexpression suppresses tumor growth in ovarian cancer via PTEN/PI3K/AKT pathway.Functional & integrative genomics · 2024Article
- MiR-17-5p-engineered sEVs Encapsulated in GelMA Hydrogel Facilitated Diabetic Wound Healing by Targeting PTEN and p21.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Unraveling the Role of Endothelial Dysfunction in Osteonecrosis of the Femoral Head: A Pathway to New Therapies.Biomedicines · 2024Review
- Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.Frontiers in endocrinology · 2024Article
- Endothelial Cell-Derived Exosomes Inhibit Osteoblast Apoptosis and Steroid-Induced Necrosis of Femoral Head Progression by Activating the PI3K/Akt/Bcl-2 Pathway.Journal of tissue engineering and regenerative medicine · 2024Article
- Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells.Biomolecules · 2023Review
- Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundGlucocorticoid (GC)-associated osteonecrosis of the femoral head (ONFH) is the most common in non-traumatic ONFH. Despite a strong relationship between GC and ONFH, the detailed mechanisms have remained elusive. Recent studies have shown that GC could directly injure the blood vessels and reduce blood supply in the femoral head. Endothelial progenitor cells (EPCs), which were inhibited quantitatively and functionally during ONFH, play an important role in maintaining the normal structure and function of vascular endothelium. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that promotes cell apoptosis, and its expression was found to be elevated in GC-associated ONFH patients. However, whether direct inhibition of PTEN attenuates GC-associated apoptosis and dysfunction of the EPCs remains largely unknown.
methodsWe investigated the effect of, VO-OHpic, a potent inhibitor of PTEN, in attenuating GC-associated apoptosis and dysfunction of EPCs and the molecular mechanism. SD rats were used to study the effect of VO-OHpic on angiogenesis and osteonecrosis in vivo.
resultsThe results revealed that methylprednisolone (MPS) obviously inhibit angiogenesis of EPCs by inducing apoptosis, destroying the normal mitochondrial structure, and disrupting function of mitochondria. VO-OHpic treatment is able to reverse the harmful effects by inhibiting the mitochondrial apoptosis pathway and activating the NF-E2-related factor 2 (Nrf2) signaling. Si-Nrf2 transfection significantly reduced the protective effects of VO-OHpic on EPCs. Our in vivo studies also showed that intraperitoneal injection of VO-OHpic obviously attenuates the osteonecrosis of the femoral head induced by MPS and potently increases the blood supply in the femoral head.
conclusionTaken together, the data suggests that inhibition of PTEN with VO-OHpic attenuates apoptosis and promotes angiogenesis of EPCs in vitro via activating Nrf2 signaling pathway and inhibiting the mitochondrial apoptosis pathway. Moreover, VO-OHpic also mitigates GC-associated ONFH and potentiates angiogenesis in the femoral head.
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