ArticleJournal of bone and mineral metabolism2015
Hypoxia enhances glucocorticoid-induced apoptosis and cell cycle arrest via the PI3K/Akt signaling pathway in osteoblastic cells.
Article in Journal of bone and mineral metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Association of TNF-α-308(G/A) and -238(G/A) polymorphisms with non-traumatic osteonecrosis of the femoral head risks: a meta-analysis.International orthopaedics · 2018Pooled it
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- egr1 and egr4 regulate zebrafish renal regeneration by promoting foxm1 expression.Journal of molecular cell biology · 2026Article
- Hypoxia and Tissue Regeneration: Adaptive Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Curculigoside is a Promising Osteoprotective Agent for Osteoporosis: Review.Drug design, development and therapy · 2025Review
- [Basic Research on the Microstructure of Rat Bones in the High-Altitude Environment of Qinghai-Tibet Plateau].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- [Akt2 inhibitor promotes M2 macrophage polarization in rats with periapical inflammation by reducing miR-155-5p expression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Phase-contrast imaging with synchrotron hard X-ray reveals the effect of icariin on bone tissue morphology and microstructure in rabbits with early glucocorticoid-induced osteonecrosis of the femoral head.Frontiers in cell and developmental biology · 2023Article
- Analysis of Bone Histomorphometry in Rat and Guinea Pig Animal Models Subject to Hypoxia.International journal of molecular sciences · 2022Article
- Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling.International journal of molecular sciences · 2022Review
- Bioinformatics Analysis of the Key Genes and Pathways in Multiple Myeloma.International journal of general medicine · 2022Article
- [Expression of Ras-Associated Protein 1 in the Vascular Endothelium of Bone Tissue with Non-Traumatic Osteonecrosis of Femoral Head].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway.Open life sciences · 2021Article
- Effects of hypoxia environment on osteonecrosis of the femoral head in Sprague-Dawley rats.Journal of bone and mineral metabolism · 2020Article
- EDNRB Reverses Methylprednisolone-Mediated Decrease in Neural Progenitor Cell Viability via Regulating PI3K/Akt Pathway and lncRNA Expression.Journal of molecular neuroscience : MN · 2020Article
- A Network Pharmacology Approach to Estimate the Active Ingredients and Potential Targets of Cuscutae semen in the Treatment of Osteoporosis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Enhancement of Intracellular Calcium Ion Mobilization by Moderately but Not Highly Positive Material Surface Charges.Frontiers in bioengineering and biotechnology · 2020Article
- Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head.International journal of biological sciences · 2020Article
- Enteric Microbiota⁻Gut⁻Brain Axis from the Perspective of Nuclear Receptors.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although osteonecrosis of the femoral head is a known primary limitation of long-term or high-dose clinical administration of glucocorticoids, the mechanisms underlying this side effect remain unclear. Hypoxia is an important biological state under numerous pathological conditions. In this study, we investigated glucocorticoid-induced osteonecrosis under hypoxic conditions in the MC3T3-E1 osteoblast cell line using a cell cytotoxicity assay, flow cytometry, and western blotting. 6α-Methylprednisolone sodium succinate (MPSL) more effectively induced apoptosis and G0/G1 arrest of MC3T3-E1 osteoblasts under hypoxic conditions than under normoxic conditions. Correspondingly, MPSL more effectively upregulated cellular levels of cleaved caspase 3, p53, and its target p21, and downregulated cyclin D1 levels in hypoxia. Moreover, overexpression of Akt abrogated the MPSL activation of p53, p21, and cleaved caspase 3 and the attenuation of cyclin D1 expression and rescued osteoblasts from MPSL-induced cell cycle arrest and apoptosis, indicating that phosphatidylinositol 3-kinase (PI3K)/Akt signaling might play an essential role in MPSL-induced inhibition of osteoblasts. Furthermore, the suppression of PI3K/Akt signaling and upregualtion of cellular p85α monomer levels by MPSL were more pronounced under hypoxic conditions than under normoxic conditions. Finally, we found that the enhancement of the effects of MPSL under hypoxic conditions was attributed to hypoxia-upregulated glucocorticoid receptor activity. In conclusion, our results demonstrate that MPSL, a synthetic glucocorticoid receptor agonist, promotes the level of p85α and inhibits PI3K/Akt signaling to induce apoptosis and cell cycle arrest in osteoblasts, and that this effect is enhanced under hypoxic conditions.
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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.