ArticleStem cell research & therapy2022
C/EBPα regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPARγ signalling pathway.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- From Mechanism to Therapy: Establishing an Integrated Framework for the Regulation and Intervention of Matrix Vesicles in Vascular Calcification.Cardiovascular drugs and therapy · 2026Review
- Time-course ATAC-seq and RNA-seq analysis of porcine synovium-derived mesenchymal stem cells under in vitro osteogenic induction.Epigenetics & chromatin · 2026Article
- Harmine ameliorates steroid-induced osteonecrosis of the femoral head by modulating metabolism and ferroptosis via HIF1-α.Fundamental research · 2026Article
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- The role of post-translational modifications in osteonecrosis of the femoral head.Frontiers in cell and developmental biology · 2026Review
- Bone and muscle crosstalk in steroid-induced osteonecrosis of the femoral head: a four-axis pathophysiological framework.Frontiers in immunology · 2026Review
- miR-199a-3p Promotes Adipogenic Differentiation to Aggravate Steroid-Induced Osteonecrosis of Femoral Head via the ITGB8/FAK-ERK/RUNX2 Pathway.Research (Washington, D.C.) · 2026Article
- Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes.Journal of translational medicine · 2025Review
- Knowledge mapping of core decompression in osteonecrosis of the femoral head: a bibliometric analysis.Annals of medicine and surgery (2012) · 2025Review
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Analysis of Animal Models of Traumatic Osteonecrosis of the Femoral Head Based on Blood Supply: A Literature Review.Orthopaedic surgery · 2025Review
- HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Quantitation of global histone post-translational modifications reveal anti-inflammatory epigenetic mechanisms of liquiritigenin based on the optimized super-SILAC strategy.Frontiers in cell and developmental biology · 2025Article
- BMDB: An integrated database and web platform for single-cell transcriptomic profiling of bone marrow microenvironment.Computational and structural biotechnology journal · 2025Article
- Pathological mechanisms and related markers of steroid-induced osteonecrosis of the femoral head.Annals of medicine · 2024Review
- Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz.Journal of nanobiotechnology · 2024Article
- Preliminary study of the role of histone deacetylase (HDAC) in steroid-induced avascular necrosis of the femoral head induced by BMSC adipogenic differentiation.Journal of orthopaedic surgery and research · 2024Article
- Aucubin suppresses TLR4/NF-κB signalling to shift macrophages toward M2 phenotype in glucocorticoid-associated osteonecrosis of the femoral head.Journal of cellular and molecular medicine · 2024Article
- Advances in the Pathogenesis of Steroid-Associated Osteonecrosis of the Femoral Head.Biomolecules · 2024Review
- 17 variants interaction of Wnt/β-catenin pathway associated with development of osteonecrosis of femoral head in Chinese Han population.Scientific reports · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe imbalance of osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is closely related to steroid-induced avascular necrosis of the femoral head (SANFH). We aimed to investigate the epigenetic mechanism of intramedullary fat accumulation and continuous osteonecrosis after glucocorticoid (GC) withdrawal in SANFH.
methodsAn SANFH model was established in SD rats, which received an intermittent high GC dose for the first 4 weeks followed by an additional 4 weeks without GC. We explored the synergistic effects and mechanisms of C/EBPα and PPARγ on the differentiation of BMSCs by lentivirus-mediated gene knockdown and overexpression assays. A chromatin immunoprecipitation assay was performed to identify epigenetic modification sites on PPARγ in vivo and in vitro.
resultsIn the SANFH model, intramedullary fat was significantly increased, and the transcription factors C/EBPα and PPARγ were upregulated simultaneously in the femoral head. In vitro, C/EBPα promoted adipogenic differentiation of BMSCs by targeting the PPARγ signalling pathway, while overexpression of C/EBPα significantly impaired osteogenic differentiation. Further studies demonstrated that histone H3K27 acetylation of PPARγ played an important role in the epigenetic mechanism underlying SANFH. C/EBPα upregulates the histone H3K27 acetylation level in the PPARγ promoter region by inhibiting HDAC1. Additionally, inhibiting the histone acetylation level of PPARγ effectively prevented adipogenic differentiation, thus slowing the progression of SANFH.
conclusionsOur results demonstrate the molecular mechanism by which C/EBPα regulates PPARγ expression by acetylating histones and revealed the epigenetic phenomenon in SANFH for the first time.
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