ArticleBone research2021
The KDM4B-CCAR1-MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis.
Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- A peroxiredoxin 1-reactive oxygen species feedback loop modulates nuclear factor kappa B activity in osteoclastogenesis.Molecular biomedicine · 2026Article
- KDM4B/DHX9 promotes chemoresistance in small-cell lung cancer through the MYCN-driven signaling pathway.Oncogene · 2026Article
- Plant Transformation States and Exposure Architecture: A Pharmacokinetic Framework for Plant-Derived Compounds in Bone Remodeling.Plants (Basel, Switzerland) · 2026Review
- d-amino acids restrain macrophage IL-1β release through gasdermin D acetylation.Science advances · 2026Article
- Hells protects mitochondrial integrity via Nr2f2 suppression during osteoclast differentiation.Cell communication and signaling : CCS · 2026Article
- Histone arginine demethylase JMJD7 promotes bone formation through regulating α-Ketoglutarate metabolism.Cell death and differentiation · 2026Article
- Histone demethylase KDM4B epigenetically controls NLRP3 expression to enhance inflammatory responses.EMBO molecular medicine · 2026Article
- KDM4B modulates ERα signaling pathway to participate in vascular smooth muscle cell calcification.Cell death discovery · 2025Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Denatonium inhibits RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype by blocking p65 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Preliminary identification of somatic mutations profile in ACL injury.Scientific reports · 2024Article
- Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.Chinese medicine · 2024Article
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.Aging cell · 2024Review
- Exploring epigenetic strategies for the treatment of osteoporosis.Molecular biology reports · 2024Review
- Histone demethylase KDM7A regulates bone homeostasis through balancing osteoblast and osteoclast differentiation.Cell death & disease · 2024Article
- KDM4B: A promising oncology therapeutic target.Cancer science · 2024Review
- TMBIM6 deficiency leads to bone loss by accelerating osteoclastogenesis.Redox biology · 2023Article
- BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism.Nature communications · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone undergoes a constant and continuous remodeling process that is tightly regulated by the coordinated and sequential actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Recent studies have shown that histone demethylases are implicated in osteoblastogenesis; however, little is known about the role of histone demethylases in osteoclast formation. Here, we identified KDM4B as an epigenetic regulator of osteoclast differentiation. Knockdown of KDM4B significantly blocked the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. Mice with myeloid-specific conditional knockout of KDM4B showed an osteopetrotic phenotype due to osteoclast deficiency. Biochemical analysis revealed that KDM4B physically and functionally associates with CCAR1 and MED1 in a complex. Using genome-wide chromatin immunoprecipitation (ChIP)-sequencing, we revealed that the KDM4B-CCAR1-MED1 complex is localized to the promoters of several osteoclast-related genes upon receptor activator of NF-κB ligand stimulation. We demonstrated that the KDM4B-CCAR1-MED1 signaling axis induces changes in chromatin structure (euchromatinization) near the promoters of osteoclast-related genes through H3K9 demethylation, leading to NF-κB p65 recruitment via a direct interaction between KDM4B and p65. Finally, small molecule inhibition of KDM4B activity impeded bone loss in an ovariectomized mouse model. Taken together, our findings establish KDM4B as a critical regulator of osteoclastogenesis, providing a potential therapeutic target for osteoporosis.
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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.