ArticleThe Journal of biological chemistry2016
Enhancer of Zeste Homolog 2 Inhibition Stimulates Bone Formation and Mitigates Bone Loss Caused by Ovariectomy in Skeletally Mature Mice.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 94 citations in OpenAlex.
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- Changing landscape of hematopoietic and mesenchymal cells and their interactions during aging and in age-related skeletal pathologies.Mechanisms of ageing and development · 2025Review
- The CHD Protein, Kismet, Restricts Synaptic BMP Signaling at Glutamatergic Synapses.Neuroscience insights · 2025Article
- Dynamic strain and β-catenin mediated suppression of interferon responsive genes in quiescent mesenchymal stromal/stem cells.Biochemistry and biophysics reports · 2024Article
- Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sensory Nerve Regulation via H3K27 Demethylation Revealed in Akermanite Composite Microspheres Repairing Maxillofacial Bone Defect.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploring epigenetic strategies for the treatment of osteoporosis.Molecular biology reports · 2024Review
- AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.Journal of cellular physiology · 2024Article
- A mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition.JCI insight · 2024Article
- Chronological analysis of periodontal bone loss in experimental periodontitis in mice.Clinical and experimental dental research · 2023Article
- Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation.Bone reports · 2023Article
- Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application.Journal of cancer research and clinical oncology · 2023Review
- Article
- Dysregulation of histone modifications in bone marrow mesenchymal stem cells during skeletal ageing: roles and therapeutic prospects.Stem cell research & therapy · 2023Review
- CTR9 drives osteochondral lineage differentiation of human mesenchymal stem cells via epigenetic regulation of BMP-2 signaling.Science advances · 2022Article
- Guanylyl Cyclase-B Dependent Bone Formation in Mice is Associated with Youth, Increased Osteoblasts, and Decreased Osteoclasts.Calcified tissue international · 2022Article
- MicroRNA-101a enhances trabecular bone accrual in male mice.Scientific reports · 2022Article
- Epigenetic Crosstalk between Malignant Plasma Cells and the Tumour Microenvironment in Multiple Myeloma.Cancers · 2022Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Perturbations in skeletal development and bone degeneration may result in reduced bone mass and quality, leading to greater fracture risk. Bone loss is mitigated by bone protective therapies, but there is a clinical need for new bone-anabolic agents. Previous work has demonstrated that Ezh2 (enhancer of zeste homolog 2), a histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation of osteogenic progenitors. Here, we investigated whether inhibition of Ezh2 can be leveraged for bone stimulatory applications. Pharmacologic inhibition and siRNA knockdown of Ezh2 enhanced osteogenic commitment of MC3T3 preosteoblasts. Next generation RNA sequencing of mRNAs and real time quantitative PCR profiling established that Ezh2 inactivation promotes expression of bone-related gene regulators and extracellular matrix proteins. Mechanistically, enhanced gene expression was linked to decreased H3K27 trimethylation (H3K27me3) near transcriptional start sites in genome-wide sequencing of chromatin immunoprecipitations assays. Administration of an Ezh2 inhibitor modestly increases bone density parameters of adult mice. Furthermore, Ezh2 inhibition also alleviated bone loss in an estrogen-deficient mammalian model for osteoporosis. Ezh2 inhibition enhanced expression of Wnt10b and Pth1r and increased the BMP-dependent phosphorylation of Smad1/5. Thus, these data suggest that inhibition of Ezh2 promotes paracrine signaling in osteoblasts and has bone-anabolic and osteoprotective potential in adults.
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Registered trials
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.