ArticleClinical and translational medicine2022
Melatonin enhances osteoblastogenesis of senescent bone marrow stromal cells through NSD2-mediated chromatin remodelling.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- Effects of melatonin and vitamin E on bone healing following alloplastic grafting in osteoporotic cranial bone defects: an experimental study.BMC oral health · 2026Article
- Mechanical Stimulation Drives Multicellular Synergy and Signaling Pathways in Developing Skeletal Tissues.Sports medicine (Auckland, N.Z.) · 2026Review
- Application Strategies of Bone Marrow Mesenchymal Stromal Cells in Bone-Related Diseases.Cell proliferation · 2026Review
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- mStem cell research & therapy · 2026Article
- Bone Marrow Mesenchymal Stem Cell Senescence in the Development of Osteoporosis: Mechanisms, Interventions, and Future Directions.Current molecular medicine · 2026Review
- Steap4 Promotes Senile Osteoporosis via FeAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- 4-Octyl Itaconate Attenuates Postmenopausal Osteoporosis by Inhibiting Ferroptosis and Enhancing Osteogenesis via the Nrf2 Pathway.Inflammation · 2025Article
- The Role of Senolytics in Osteoporosis.Biomolecules · 2025Review
- Beyond natural silk: Bioengineered silk fibroin for bone regeneration.Materials today. Bio · 2025Review
- Melatonin: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms.Journal of pineal research · 2025Review
- Epigenetic Control of Osteogenesis: Pathways Toward Improved Bone Regeneration.Current osteoporosis reports · 2025Review
- Antisenescence therapies for age-related bone loss: Target factors, medicines, biomedical materials.Clinical and translational medicine · 2025Review
- HRP2 regulating MICU1-mediated CaNeoplasia (New York, N.Y.) · 2025Article
- GRAMMAR-Lambda Delivers Efficient Understanding of the Genetic Basis for Head Size in Catfish.Biology · 2025Article
- Aberrant Tryptophan Metabolism Manipulates Osteochondral Homeostasis.Research (Washington, D.C.) · 2025Review
- Quercetin ameliorates senescence and promotes osteogenesis of BMSCs by suppressing the repetitive element‑triggered RNA sensing pathway.International journal of molecular medicine · 2025Article
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Authors and funding
20 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundAging-associated osteoporosis is frequently seen in the elderly in clinic, but efficient managements are limited because of unclear nosogenesis. The current study aims to investigate the role of melatonin on senescent bone marrow stromal cells (BMSCs) and the underlying regulating mechanism.
methodsMelatonin levels were tested by ELISA. Gene expression profiles were performed by RNA-sequencing, enrichment of H3K36me2 on gene promoters was analyzed by Chromatin Immunoprecipitation Sequencing (ChIP-seq), and chromatin accessibility was determined by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). Osteogenesis of BMSCs in vitro was measured by Alizarin Red and Alkaline Phosphatase staining, and in vivo effects of melatonin was assessed by histological staining and micro computed tomography (micro-CT) scan. Correlation of NSD2 expression and severity of senile osteoporosis patients were analyzed by Pearson correlation.
resultsMelatonin levels were decreased during aging in human bone marrow, accompanied by downregulation of the histone methyltransferase nuclear receptor binding SET domain protein 2 (NSD2) expression in the senescent BMSCs. Melatonin stimulated the expression of NSD2 through MT1/2-mediated signaling pathways, resulting in the rebalancing of H3K36me2 and H3K27me3 modifications to increase chromatin accessibility of the osteogenic genes, runt-related transcription factor 2 (RUNX2) and bone gamma-carboxyglutamate protein (BGLAP). Melatonin promoted osteogenesis of BMSCs in vitro, and alleviates osteoporosis progression in the aging mice. In clinic, severity of senile osteoporosis (SOP) was negatively correlated with melatonin level in bone marrow, as well as NSD2 expression in BMSCs. Similarly, melatonin remarkably enhanced osteogenic differentiation of BMSCs derived from SOP patients in vitro.
conclusionsCollectively, our study dissects previously unreported mechanistic insights into the epigenetic regulating machinery of melatonin in meliorating osteogenic differentiation of senescent BMSC, and provides evidence for application of melatonin in preventing aging-associated bone loss.
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