ArticleEpigenetics2017
Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis.
Article in Epigenetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 79 citations in OpenAlex.
- Lgr6Genes & diseases · 2026Review
- Epigenetic Patterns in Musculoskeletal Disease: Methylation ofCurrent issues in molecular biology · 2026Article
- Altered lineage commitment of bone marrow mesenchymal stem cells in idiopathic osteonecrosis of the femoral head.World journal of orthopedics · 2025Article
- Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Epigenetic modulation of the NLRP6 inflammasome sensor as a therapeutic modality to reduce necroptosis-driven gastrointestinal mucosal dysfunction in HIV/SIV infection.Cell communication and signaling : CCS · 2025Article
- Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis.Stem cell research & therapy · 2025Article
- Article
- Variance-components tests for genetic association with multiple interval-censored outcomes.Statistics in medicine · 2024Article
- Dnmt3b ablation affects fracture repair process by regulating apoptosis.BMC musculoskeletal disorders · 2024Article
- FOXC1 Promotes Osteoblastic Differentiation of Bone Marrow Mesenchymal Stem Cells via the Dnmt3b/CXCL12 Axis.Biochemical genetics · 2024Article
- Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.Frontiers in genetics · 2024Review
- The essential roles of mGenes & diseases · 2024Review
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study.BMC medical genomics · 2023Article
- Engineering a Pro-Osteogenic Secretome through the Transient Silencing of the Gene Encoding Secreted Frizzled Related Protein 1.International journal of molecular sciences · 2023Article
- Review
- Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing.Bone · 2023Article
- Review
- Effects of Systemic or Local Administration of Mesenchymal Stem Cells from Patients with Osteoporosis or Osteoarthritis on Femoral Fracture Healing in a Mouse Model.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation.
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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.