ArticleCellular and molecular life sciences : CMLS2020
Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Epigenetic Regulation of Bone Homeostasis in Osteoporosis: Mechanisms, Evidence Gaps, and Translational Prospects.Cell biochemistry and function · 2026Review
- Knockout of kdm4aa inhibits early embryonic development in zebrafish via downregulating cyp26a1.Molecular genetics and genomics : MGG · 2026Article
- Core microRNAs regulate neural crest delamination and condensation in the developing trigeminal ganglion.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications.Cell death & disease · 2025Review
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- JIB-04 improves PPARγ expression and enhances adipogenic differentiation efficiency in human umbilical cord mesenchymal stem cells.Biochemistry and biophysics reports · 2025Article
- Exome sequencing of patients with syndromic tall stature reveals four novel candidate genes.Endocrine connections · 2025Article
- Review
- Parental benzo[a]pyrene exposure impacts histone modifications in osteoblast subpopulations.Environmental epigenetics · 2025Article
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation.World journal of stem cells · 2024Review
- Epigenetic Regulation of Autophagy in Bone Metabolism.Function (Oxford, England) · 2024Review
- Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.Frontiers in genetics · 2024Review
- Loss of N-acetylglucosaminyl transferase V is involved in the impaired osteogenic differentiation of bone marrow mesenchymal stem cells.Experimental animals · 2023Article
- Dysregulation of histone modifications in bone marrow mesenchymal stem cells during skeletal ageing: roles and therapeutic prospects.Stem cell research & therapy · 2023Review
- MiR-137 promotes TLR4/NF-κB pathway activity through targeting KDM4A, inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis.Journal of orthopaedic surgery and research · 2023Article
- Oridonin Attenuates Thioacetamide-Induced Osteoclastogenesis Through MAPK/NF-κB Pathway and Thioacetamide-Inhibited Osteoblastogenesis Through BMP-2/RUNX2 Pathway.Calcified tissue international · 2023Article
- The role of wnt signaling in diabetes-induced osteoporosis.Diabetology & metabolic syndrome · 2023Review
- Atf7ip Inhibits Osteoblast Differentiation via Negative Regulation of the Sp7 Transcription Factor.International journal of molecular sciences · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and established stromal ST2 line. Overexpression of wild-type Kdm4a promoted adipogenic differentiation and blocked osteogenic differentiation of the progenitor cells. This effect was largely alleviated when the catalytically dead mutation was made. Conversely, depletion or inactivation of Kdm4a in undifferentiated progenitor cells inhibited the formation of adipocytes and promoted the differentiation of osteoblasts. Mechanism explorations showed that overexpression of Kdm4a upregulated the expression of secreted frizzled-related protein 4 (Sfrp4) and CCAAT/enhancer-binding protein α (C/ebpα). Chromatin immunoprecipitation assay demonstrated that KDM4A directly bound the promoters of Sfrp4 and C/ebpα, removed the histone methylation mark H3K9me3, and reduced DNA methylation levels of CpG in promoter regions of C/ebpα and Sfrp4. Furthermore, overexpression of Kdm4a inactivated canonical Wnt signaling. Moreover, activation of canonical Wnt signaling through silencing of Sfrp4 in ST2 attenuated the inhibition of osteogenic differentiation and the enhancement of adipogenic differentiation by KDM4A. These data have identified KDM4A as a novel regulator of osteoblast and adipocyte differentiation and suggest KDM4A inhibition as a potential therapeutic target for treating metabolic disorders such as osteoporosis.
Indexed as
Identifiers
What OpenQuestion holds
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.