ArticleStem cell research & therapy2023
Exogenous melatonin ameliorates steroid-induced osteonecrosis of the femoral head by modulating ferroptosis through GDF15-mediated signaling.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- Aerobic Exercise-Mediated Regulation of Ferroptosis in Skeletal Disorders: Molecular Mechanisms and Potential Applications.Biomolecules · 2026Review
- Alpha-2-macroglobulin attenuates glucocorticoid-induced osteonecrosis of the femoral head by enhancing osteogenesis and antioxidant defense via the Akt/Nrf2 signaling pathway.Journal of molecular histology · 2026Article
- Tanshinone I Represses Ferroptosis to Protect Against Steroid-Induced Osteonecrosis of the Femoral Head by Activating the Nrf2/SLC7A11 Axis.Biochemical genetics · 2026Article
- Melatonin improves osteogenic differentiation in a high-glucose environment by activating NRF2 to promote autophagy through the regulation of cross-talk between macrophages and bone marrow mesenchymal stem cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- piR-27222 alleviates dexamethasone-induced osteoporosis by inhibiting ferroptosis through modulating WWP1.Journal of orthopaedic surgery and research · 2026Article
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- Article
- Progress of Programmed Cell Death in Steroid-Induced Osteonecrosis of the Femoral Head.Orthopaedic surgery · 2026Review
- Steap4 Promotes Senile Osteoporosis via FeAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Melatonin Attenuates Spinal Cord Injury by Regulating Ferroptosis Through the Nrf2/HO-1/GPX4 Pathway.Molecular neurobiology · 2025Article
- PARP inhibitor BMN673 triggers PARylation-mediated ATF4-GDF15 pathway to drive autophagy and ferroptosis in ataxia telangiectasia mutated gene-deficient colorectal cancer cells.Molecular biomedicine · 2025Article
- Effects and mechanisms of MSCs and MSC-derived exosomes in regulating ferroptosis.Journal of physiology and biochemistry · 2025Review
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- Identification and validation of SQLE in steroid-induced osteonecrosis of the femoral head: a bioinformatics and experimental study.Journal of orthopaedic surgery and research · 2025Article
- YTHDF3-associated m6A regulation and cuproptosis-related gene expression in steroid-induced osteonecrosis of the femoral head.Journal of molecular histology · 2025Article
- microRNA-576-5p ameliorates dexamethasone-induced BMSC injury by suppressing ANXA2.Scientific reports · 2025Article
- Upregulated GDF-15 in Ankylosing Spondylitis: Pathologic Ossification Promotion through Ligament Fibroblast Osteogenic Differentiation.ACR open rheumatology · 2025Article
- PSMD14 Stabilizes SLC7A11 to Ameliorate Glucocorticoid-Induced Osteoporosis by Suppressing Osteocyte Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFerroptosis is an iron-related form of programmed cell death. Accumulating evidence has identified the pathogenic role of ferroptosis in multiple orthopedic disorders. However, the relationship between ferroptosis and SONFH is still unclear. In addition, despite being a common disease in orthopedics, there is still no effective treatment for SONFH. Therefore, clarifying the pathogenic mechanism of SONFH and investigating pharmacologic inhibitors from approved clinical drugs for SONFH is an effective strategy for clinical translation. Melatonin (MT), an endocrine hormone that has become a popular dietary supplement because of its excellent antioxidation, was supplemented from an external source to treat glucocorticoid-induced damage in this study.
methodsMethylprednisolone, a commonly used glucocorticoid in the clinic, was selected to simulate glucocorticoid-induced injury in the current study. Ferroptosis was observed through the detection of ferroptosis-associated genes, lipid peroxidation and mitochondrial function. Bioinformatics analysis was performed to explore the mechanism of SONFH. In addition, a melatonin receptor antagonist and shGDF15 were applied to block the therapeutic effect of MT to further confirm the mechanism. Finally, cell experiments and the SONFH rat model were used to detect the therapeutic effects of MT.
resultsMT alleviated bone loss in SONFH rats by maintaining BMSC activity through suppression of ferroptosis. The results are further verified by the melatonin MT2 receptor antagonist that can block the therapeutic effects of MT. In addition, bioinformatic analysis and subsequent experiments confirmed that growth differentiation factor 15 (GDF15), a stress response cytokine, was downregulated in the process of SONFH. On the contrary, MT treatment increased the expression of GDF15 in bone marrow mesenchymal stem cells. Lastly, rescue experiments performed with shGDF15 confirmed that GDF15 plays a key role in the therapeutic effects of melatonin.
conclusionsWe proposed that MT attenuated SONFH by inhibiting ferroptosis through the regulation of GDF15, and supplementation with exogenous MT might be a promising method for the treatment of SONFH.
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