ArticleCell death & disease2018
The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects against osteoporosis.
Article in Cell death & disease, 2018. 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, 64 citations in OpenAlex.
- Wilforine attenuates inflammatory osteolysis by suppressing osteoclast fusion through JAK-STAT-stomatin immunoregulatory signaling.Frontiers in immunology · 2026Article
- New insights into methionine's role in maintaining intestinal stem cell regeneration via autophagy regulation.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Review
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- Modulating Osteoclast Activity and Immune Responses with Ultra-Low-Dose Silver Nanoparticle-Loaded TiOJournal of functional biomaterials · 2025Article
- Dot1l Regulates the Spontaneous Bone Regeneration of Periosteum-Derived Stem Cells by Regulating Chac1 Expression.Stem cells international · 2025Article
- Vagus nerve stimulation alleviates alveolar bone loss and inflammation in ligature-induced periodontitis rat model.Journal of applied oral science : revista FOB · 2025Article
- Loss of RNA-binding protein CELF2 promotes acute leukemia development via FAT10-mTORC1.Oncogene · 2024Article
- The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.Histology and histopathology · 2024Review
- Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.Aging cell · 2024Review
- Epigenetic Regulation of Autophagy in Bone Metabolism.Function (Oxford, England) · 2024Review
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study.Signal transduction and targeted therapy · 2023Review
- Comprehensive analysis of epigenetics mechanisms in osteoporosis.Frontiers in genetics · 2023Review
- MiR-152-5p suppresses osteogenic differentiation of mandible mesenchymal stem cells by regulating ATG14-mediated autophagy.Stem cell research & therapy · 2022Article
- Article
- Recent advances in epigenetic anticancer therapeutics and future perspectives.Frontiers in genetics · 2022Review
- Role of histone modification in the occurrence and development of osteoporosis.Frontiers in endocrinology · 2022Review
- Mn-containing bioceramics inhibit osteoclastogenesis and promote osteoporotic bone regeneration via scavenging ROS.Bioactive materials · 2021Article
- Recent advances in the epigenetics of bone metabolism.Journal of bone and mineral metabolism · 2021Review
- Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress.Oxidative medicine and cellular longevity · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL-induced RAW264.7 macrophage cells as an osteoclast differentiation model, we found that DOT1L and H3K79me2 levels were upregulated during osteoclast differentiation. Small molecule inhibitor- (EPZ5676 or EPZ004777) or short hairpin RNA-mediated reduction in DOT1L expression promoted osteoclast differentiation and resorption. In addition, DOT1L inhibition increased osteoclast surface area and accelerated bone-mass reduction in a mouse ovariectomy (OVX) model of osteoporosis without alter osteoblast differentiation. DOT1L inhibition increase reactive oxygen species (ROS) generation and autophagy activity, and cell migration in pre-osteoclasts. Moreover, it strengthened expression of osteoclast fusion and resorption-related protein CD9 and MMP9 in osteoclasts derived from RAW264.7. Our findings support a new mechanism of DOT1L-regulated, H3K79me2-mediated, epigenetic regulation of osteoclast differentiation, implicating DOT1L as a new therapeutic target for osteoclast dysregulation-induced disease.
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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.