ArticlePloS one2015
Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
194 citing papers in PubMed, 1 synthesis or guideline pooled it, 311 citations in OpenAlex.
- Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis.Frontiers in immunology · 2021Pooled it
- From farm to lab: gene-edited sheep transforming bone research.JBMR plus · 2026Review
- Critical Overview of Molecular Insights into Osteoarthritis and Therapeutic Targets: Cytokines, RANKL, MMPs, Adipokines and Phosphate Dysregulation.International journal of molecular sciences · 2026Review
- A RANKLBone research · 2026Article
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Osteoimmunology: Can We Prevent Bone Loss in Rheumatoid Arthritis with Modern Antirheumatic Drugs?Calcified tissue international · 2026Review
- Recent progress in immunomodulation-based strategies for bone repair.Regenerative therapy · 2026Review
- Generation and characterization of a novel inducible Sost_P2A_CreERT2 mouse model with high specificity for osteocytes.JBMR plus · 2026Article
- The Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Bone Metabolism.International journal of molecular sciences · 2026Review
- Lipocalin-2 upregulation in hypoxic murine osteocytes enhances RANKL-induced osteoclastogenesis.Scientific reports · 2026Article
- Identification and Mechanisms of Osteocyte Subsets Involved in the Pathological Progression of Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role and mechanisms of bone microenvironment regulators in osteoporosis: novel intervention strategies for addressing the challenges of aging.Frontiers in endocrinology · 2026Review
- Crosstalk Between Hematopoietic and Mesenchymal Cells in Bone and Tooth Immune Response.Advances in experimental medicine and biology · 2026Review
- Bone regenerative efficacy of binder-jet fabricated hydroxyapatite granules with and without biomimetic octacalcium phosphate-coated modification in a rat critical-sized calvarial defect model.Regenerative biomaterials · 2026Article
- Bone marrow adipoq-lineage cells in regulating the bone and marrow microenvironment: identities, functions, and mechanisms.Frontiers in endocrinology · 2026Review
- Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential.Frontiers in immunology · 2026Review
- Ferroptosis in osteoporosis: core mechanisms, cell-specific effects in bone remodelling, and therapeutic perspectives.Frontiers in endocrinology · 2026Review
- Exploring osteomicrobiology: A narrative review of the gut-bone axis in osteoporosis.Irish journal of medical science · 2025Review
- Article
- Recent Advances in the Role of Osteocytes in Orthodontic Tooth Movement.International journal of molecular sciences · 2025Review
134 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The cytokine receptor activator of nuclear factor kappa B ligand (RANKL), encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone.
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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.