ArticleCell metabolism2015
Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway.
Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 167 citations in OpenAlex.
- Effects of a single-dose denosumab on glucose and lipid homeostasis in young infertile men.Endocrine · 2026Trial
- Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.Nature communications · 2020Trial
- Effects of Common Food Additives Kappa-, Iota- and Lambda-Carrageenans on Intestinal Epithelial Cell Activation and Barrier Disruption.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Bone as an endocrine regulator of lipid and energy metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Smart biomaterials for skeletal aging repair and regeneration.Bone research · 2026Review
- A Microphysiological Interface of Skeletal Myobundles and Inflamed Adipose Tissue for Recapitulating Muscle Dysfunction in an Obese Microenvironment.Advanced healthcare materials · 2026Article
- The Relationship Between the Polymorphisms of RANK Gene and Type 2 Diabetes Mellitus in Postmenopausal Women.Clinical medicine insights. Endocrinology and diabetes · 2026Article
- Article
- The role of bone in whole-body energy metabolism.Nature reviews. Endocrinology · 2025Review
- Drug-induced regeneration of pancreatic beta cells: An approach to cellular therapeutic targets.Cell regeneration (London, England) · 2025Review
- From Bone Health to Lifespan: Pleiotropic Effects of Antiresorptive Agents.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- RSPO1, a potent inducer of pancreatic β cell neogenesis.Cell reports. Medicine · 2025Article
- The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease.Nature reviews. Endocrinology · 2025Review
- Islet single-cell transcriptomic profiling during obesity-induced beta cell expansion in female mice.iScience · 2025Article
- Beyond Bone Remodeling: Denosumab's Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases-A Narrative Review.Biomedicines · 2025Review
- Liver-derived Neuregulin1α stimulates compensatory pancreatic β cell hyperplasia in insulin resistance.Nature communications · 2025Article
- 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
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Diabetes results from a reduction of pancreatic β-cells. Stimulating replication could normalize β-cell mass. However, adult human β-cells are recalcitrant to proliferation. We identified osteoprotegerin, a bone-related decoy receptor, as a β-cell mitogen. Osteoprotegerin was induced by and required for lactogen-mediated rodent β-cell replication. Osteoprotegerin enhanced β-cell proliferation in young, aged, and diabetic mice. This resulted in increased β-cell mass in young mice and significantly delayed hyperglycemia in diabetic mice. Osteoprotegerin stimulated replication of adult human β-cells, without causing dedifferentiation. Mechanistically, osteoprotegerin induced human and rodent β-cell replication by modulating CREB and GSK3 pathways, through binding Receptor Activator of NF-κB (RANK) Ligand (RANKL), a brake in β-cell proliferation. Denosumab, an FDA-approved osteoporosis drug, and RANKL-specific antibody induced human β-cell proliferation in vitro, and in vivo, in humanized mice. Thus, osteoprotegerin and Denosumab prevent RANKL/RANK interaction to stimulate β-cell replication, highlighting the potential for repurposing an osteoporosis drug to treat diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.