ArticleMolecular and cellular biology2006
Parathyroid hormone controls receptor activator of NF-kappaB ligand gene expression via a distant transcriptional enhancer.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 167 citations in OpenAlex.
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- Severe Hypocalcemia During JAK1/2 Inhibitor Therapy for Myelofibrosis in a Patient with Liver Cirrhosis.Internal medicine (Tokyo, Japan) · 2025Article
- Roles of osteoclasts in pathological conditions.Pathology international · 2025Review
- Molecular mechanism of bone metastasis in breast cancer.Frontiers in oncology · 2024Review
- Effects of PTH on osteoblast bioenergetics in response to glucose.Bone reports · 2023Article
- Predictive and prognostic biomarkers of bone metastasis in breast cancer: current status and future directions.Cell & bioscience · 2023Review
- Identification of an intronic enhancer regulating RANKL expression in osteocytic cells.Bone research · 2023Article
- Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.Frontiers in physiology · 2023Review
- Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study.Cancers · 2022Article
- The genomic architecture of metastasis in breast cancer: focus on mechanistic aspects, signalling pathways and therapeutic strategies.Medical oncology (Northwood, London, England) · 2021Review
- SLPI is a critical mediator that controls PTH-induced bone formation.Nature communications · 2021Article
- Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo.PloS one · 2021Article
- Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level.Journal of the Endocrine Society · 2020Article
- Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment.International journal of molecular sciences · 2019Review
- Sex-determining region Y (SRY) attributes to gender differences in RANKL expression and incidence of osteoporosis.Experimental & molecular medicine · 2019Article
- TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis.Nature communications · 2019Article
- Map and model-moving from observation to prediction in toxicogenomics.GigaScience · 2019Article
- Activation of Shc1 Allows Oncostatin M to Induce RANKL and Osteoclast Formation More Effectively Than Leukemia Inhibitory Factor.Frontiers in immunology · 2019Article
- Parathyroid hormone(1-34) and its analogs differentially modulate osteoblasticThe Journal of biological chemistry · 2018Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
RANKL, a protein essential for osteoclast development and survival, is stimulated by parathyroid hormone (PTH) via a PTH receptor 1/cyclic AMP (cAMP)/protein kinase A (PKA)/CREB cascade, exclusively in osteoblastic cells. We report that a bacterial artificial chromosome-based transcriptional reporter construct containing 120 kb of RANKL 5'-flanking region was stimulated by dibutyryl-cAMP in stromal/osteoblastic cells, but not other cell types. Full cAMP responsiveness was dependent upon a conserved 715-bp region located 76 kb upstream from the transcription start site, which we identified by sequential deletion analysis and by comparison of human and mouse genomic sequences in silico. This region contained conserved consensus sequences which bound CREB and the osteoblast-specific transcription factor Runx2, and when mutated blunted cAMP responsiveness. Overexpression of Runx2 potentiated cAMP responsiveness of the endogenous RANKL gene in a cell-type-specific manner. Lastly, PTH responsiveness of the endogenous RANKL gene was abrogated in mice from which we deleted this conserved upstream region. Thus, PTH responsiveness of the RANKL gene is determined by a distant regulatory region that responds to cAMP in a cell-type-specific manner and Runx2 may contribute to such cell-type specificity.
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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.