ArticleScience advances2023
RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Effects of a single-dose denosumab on glucose and lipid homeostasis in young infertile men.Endocrine · 2026Trial
- Human pancreatic ductal cells from non-diabetic donors function as non-professional antigen-presenting cells upon inflammatory cytokine exposure.Diabetologia · 2026Article
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- Epigenetic Regulation Involving microRNAs in Diabetes.Biomolecules · 2026Review
- Contribution of monocyte subpopulations to the pathogenesis and therapy outcome of type 1 diabetes management in pediatric patients.Frontiers in immunology · 2026Article
- Extracellular vesicles from cytokine-treated human pancreatic ductal cells enhance HLA class I expression in beta cells.Frontiers in immunology · 2026Article
- ACE2 Alleviates Microglia Neuroinflammation by RANK-RANKL-OPG Axis in Parkinson's Disease.Inflammation · 2025Article
- Plasma Proteomic Profiling Yields a High-Performance Biomarker Panel for Predicting a Poor Prognosis in Patients with COVID-19.Journal of proteome research · 2025Article
- New Evidence, Creative Insights, and Strategic Solutions: Advancing the Understanding and Practice of Diabetes Osteoporosis.Journal of diabetes · 2025Review
- Research Progress on the Influence of Novel Targeted Drugs for Osteoporosis on Glucose Metabolism.Biomolecules · 2025Review
- LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.Molecular metabolism · 2025Article
- Promotion of beta cell proliferation through DYRK kinase inhibition using the marine natural product breitfussin C.Scientific reports · 2025Article
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
- Immune mechanisms in chronic kidney disease-mineral and bone disorder: current insights and therapeutic implications.Frontiers in medicine · 2025Review
- Bacterial and host interactions inFrontiers in microbiology · 2025Review
- Regulation of protein arginine methyltransferase in osteoporosis: a narrative review.Frontiers in cell and developmental biology · 2025Review
- Extra-osseous Roles of the RANK-RANKL-OPG Axis with a Focus on Skeletal Muscle.Current osteoporosis reports · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Treatment for type 1 diabetes (T1D) requires stimulation of functional β cell regeneration and survival under stress. Previously, we showed that inhibition of the RANKL/RANK [receptor activator of nuclear factor kappa Β (NF-κB) ligand] pathway, by osteoprotegerin and the anti-osteoporotic drug denosumab, induces rodent and human β cell proliferation. We demonstrate that the RANK pathway mediates cytokine-induced rodent and human β cell death through RANK-TRAF6 interaction and induction of NF-κB activation. Osteoprotegerin and denosumab protected β cells against this cytotoxicity. In human immune cells, osteoprotegerin and denosumab reduce proinflammatory cytokines in activated T-cells by inhibiting RANKL-induced activation of monocytes. In vivo, osteoprotegerin reversed recent-onset T1D in nonobese diabetic/Ltj mice, reduced insulitis, improved glucose homeostasis, and increased plasma insulin, β cell proliferation, and mass in these mice. Serum from T1D subjects induced human β cell death and dysfunction, but not α cell death. Osteoprotegerin and denosumab reduced T1D serum-induced β cell cytotoxicity and dysfunction. Inhibiting RANKL/RANK could have therapeutic potential.
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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.