ArticleBone research2023
Identification of an intronic enhancer regulating RANKL expression in osteocytic cells.
Article in Bone research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Osteocyte parvalbumin mediates mechanotransduction to attenuate osteoarthritis.Nature communications · 2026Article
- Alterations in bone-related hormones and genes expression in femoral bone of polycystic ovary syndrome rats.Journal of bone and mineral metabolism · 2026Article
- Comparative Molecular Insights and Computational Modeling of Multiple Myeloma and Osteosarcoma.International journal of molecular sciences · 2026Review
- Medullary cavity expansion is mediated by distinct cell populations during fetal bone development.Nature communications · 2026Article
- Osteocytes regulate osteoprotegerin expression via the p38-MAPK-CREB pathway in rheumatoid arthritis.JBMR plus · 2026Article
- Enhancer-mediated Etv4 activation stimulates osteogenic differentiation.Nature communications · 2026Article
- Genes From Epithelial-Mesenchymal Transition Predict Overall Survival Effectively in Breast Cancer: A Novel Risk Model Based on Initial Step of Tumor Metastasis.Breast cancer : basic and clinical research · 2026Article
- A mechanobiological hypothesis on bone cement-induced progression of bone metastases.Frontiers in bioengineering and biotechnology · 2026Article
- Exosomal non-coding RNAs in the regulation of bone metabolism homeostasis: Molecular mechanism and therapeutic potential.Heliyon · 2025Review
- IL7-IL7R Interaction Mediates Fibroblast-Driven Macrophage-to-Osteoclast Differentiation in Periodontitis.Journal of inflammation research · 2025Article
- DeepEnhancerPPO: An Interpretable Deep Learning Approach for Enhancer Classification.International journal of molecular sciences · 2024Article
- Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for juvenile idiopathic arthritis.Journal of translational autoimmunity · 2024Article
- Active enhancers: recent research advances and insights into disease.Biology direct · 2024Review
- Crosstalk between bone and the immune system.Journal of bone and mineral metabolism · 2024Review
- Unraveling ferroptosis in osteogenic lineages: implications for dysregulated bone remodeling during periodontitis progression.Cell death discovery · 2024Article
- The neutrophil-osteogenic cell axis promotes bone destruction in periodontitis.International journal of oral science · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bony skeleton is continuously renewed throughout adult life by the bone remodeling process, in which old or damaged bone is removed by osteoclasts via largely unknown mechanisms. Osteocytes regulate bone remodeling by producing the osteoclast differentiation factor RANKL (encoded by the TNFSF11 gene). However, the precise mechanisms underlying RANKL expression in osteocytes are still elusive. Here, we explored the epigenomic landscape of osteocytic cells and identified a hitherto-undescribed osteocytic cell-specific intronic enhancer in the TNFSF11 gene locus. Bioinformatics analyses showed that transcription factors involved in cell death and senescence act on this intronic enhancer region. Single-cell transcriptomic data analysis demonstrated that cell death signaling increased RANKL expression in osteocytic cells. Genetic deletion of the intronic enhancer led to a high-bone-mass phenotype with decreased levels of RANKL in osteocytic cells and osteoclastogenesis in the adult stage, while RANKL expression was not affected in osteoblasts or lymphocytes. These data suggest that osteocytes may utilize a specialized regulatory element to facilitate osteoclast formation at the bone surface to be resorbed by linking signals from cellular senescence/death and RANKL expression.
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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.