ArticleJCI insight2020
Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Consequences of Aging on Bone.Aging and disease · 2023Pooled it
- Bone Aging and Glycative Stress: Convergent and Divergent Mechanisms Driving Skeletal Deterioration.Cells · 2026Review
- Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels.Aging cell · 2026Article
- Osteocyte-vascular Interactions in Bone Physiology and Pathology.Current osteoporosis reports · 2026Review
- Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hydrogels as Local Structural-Protective Platforms in Rheumatoid Arthritis: An Evidence-Graded Review Across the Synovium-Cartilage-Bone Axis.Gels (Basel, Switzerland) · 2026Review
- Article
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- The role and mechanisms of bone microenvironment regulators in osteoporosis: novel intervention strategies for addressing the challenges of aging.Frontiers in endocrinology · 2026Review
- Immune-metabolic convergence in skeletal remodeling disorders: shared osteoimmune, senescent and lipid mechanisms across aging-related and immune-mediated bone disease.Frontiers in immunology · 2026Review
- Osteoimmune senescence in aging bone: from inflammaging dogma to cell-type-specific therapeutic windows.Frontiers in immunology · 2026Review
- Identification and Mechanisms of Osteocyte Subsets Involved in the Pathological Progression of Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immune ageing in skeletal fragility: clonal haematopoiesis and failure of inflammatory resolution during fracture repair.Frontiers in immunology · 2026Review
- Senescent Cells Involved in Deterioration of Bone Microstructure by High-Frequency Parathyroid Hormone 1-34 Administration and Bone Loss.Aging cell · 2026Article
- Osteoimmune senescence in aging-related bone diseases.Frontiers in immunology · 2026Review
- The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.Current osteoporosis reports · 2025Review
- Biomaterials targeting senescent cells for bone regeneration: State-of-the-art and future perspectives.Bioactive materials · 2025Review
- Article
- Sex-specific transcriptomic profiling reveals key players in bone loss associated with Alzheimer's disease.GeroScience · 2025Article
18 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
14 authors at 3 institutions in 2 countries.
Funding
Abstract
In aging mice, osteoclast number increases in cortical bone but declines in trabecular bone, suggesting that different mechanisms underlie age-associated bone loss in these 2 compartments. Osteocytes produce the osteoclastogenic cytokine RANKL, encoded by Tnfsf11. Tnfsf11 mRNA increases in cortical bone of aged mice, suggesting a mechanism underlying the bone loss. To address this possibility, we aged mice lacking RANKL in osteocytes. Whereas control mice lost cortical bone between 8 and 24 months of age, mice lacking RANKL in osteocytes gained cortical bone during this period. Mice of both genotypes lost trabecular bone with age. Osteoclasts increased with age in cortical bone of control mice but not in RANKL conditional knockout mice. Induction of cellular senescence increased RANKL production in murine and human cell culture models, suggesting an explanation for elevated RANKL levels with age. Overexpression of the senescence-associated transcription factor Gata4 stimulated Tnfsf11 expression in cultured murine osteoblastic cells. Finally, elimination of senescent cells from aged mice using senolytic compounds reduced Tnfsf11 mRNA in cortical bone. Our results demonstrate the requirement of osteocyte-derived RANKL for age-associated cortical bone loss and suggest that increased Tnfsf11 expression with age results from accumulation of senescent cells in cortical 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.