ArticleJournal of cellular biochemistry2015
Correlating RANK ligand/RANK binding kinetics with osteoclast formation and function.
Article in Journal of cellular biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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
26 citing papers in PubMed, 46 citations in OpenAlex.
- Dynamic changes of Receptor activator of nuclear factor-κB expression in Circulating Tumor Cells during Denosumab predict treatment effectiveness in Metastatic Breast Cancer.Scientific reports · 2020Trial
- Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.ACS applied materials & interfaces · 2025Article
- Stephanine Protects Against Osteoporosis by Suppressing Osteoclastogenesis via Inhibition of the RANKL-RANK Interaction.Journal of cellular and molecular medicine · 2024Article
- Article
- Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-basedFrontiers in bioengineering and biotechnology · 2023Article
- AnFrontiers in bioengineering and biotechnology · 2023Article
- Inflammation-related proteomics demonstrate landscape of fracture blister fluid in patients with acute compartment syndrome.Frontiers in immunology · 2023Article
- Teff Grain-Based Functional Food for Prevention of Osteoporosis: Sensory Evaluation and Molecular Docking Approach.Plant foods for human nutrition (Dordrecht, Netherlands) · 2022Article
- N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling.Frontiers in endocrinology · 2022Article
- Calcium phosphate-based materials regulate osteoclast-mediated osseointegration.Bioactive materials · 2021Article
- PERK signaling pathway in bone metabolism: Friend or foe?Cell proliferation · 2021Review
- Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio.International journal of medical sciences · 2021Article
- Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Article
- Evaluation of Isoflavones as Bone Resorption Inhibitors upon Interactions with Receptor Activator of Nuclear Factor-κB Ligand (RANKL).Molecules (Basel, Switzerland) · 2020Article
- Inhibitory Effect of Cudratrixanthone U on RANKL-Induced Osteoclast Differentiation and Function in Macrophages and BMM Cells.Frontiers in pharmacology · 2020Article
- Creation of RANKL mutants with low affinity for decoy receptor OPG and their potential anti-fibrosis activity.The FEBS journal · 2019Article
- Effects of receptor activator nuclear factor κB gene polymorphisms on the susceptibility to knee osteoarthritis: A case-control study.Medicine · 2019Observational
- Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.Endocrine · 2018Review
- Article
- A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The interaction between Receptor Activator of NF-κB Ligand (RANKL) and its receptor RANK is essential for the differentiation and bone resorbing capacity of the osteoclast. Osteoprotegerin (OPG), a soluble homodimer, acts as a decoy receptor for RANKL and thus inhibits osteoclastogenesis. An imbalance in the RANKL/RANK/OPG axis, with decreased OPG and/or increased RANKL, is associated with diseases that favor bone loss, including osteoporosis. Recently, we established a yeast surface display system and screened libraries of randomly mutated RANKL proteins to identify mutations that abolish binding to OPG while preserving recognition of RANK. These efforts yielded several RANKL variants possessing substantially higher affinity for RANK compared to their wild-type (WT) counterpart. Using recombinant RANKL mutant proteins, we find those with increased affinity for RANK produce more robust signaling in osteoclast lineage cells and have greater osteoclastogenic potential. Our results are the first to document gain of function RANKL mutations. They indicate that the physiological RANKL/RANK interaction is not optimized for maximal signaling and function, perhaps reflecting the need to maintain receptor specificity within the tumor necrosis factor superfamily (TNFSF). Instead, we find, a biphasic relationship exists between RANKL/RANK affinity and osteoclastogenic capacity. In our panel of RANKL variants, this relationship is driven entirely by manipulation of the kinetic off-rate. Our structure-based and yeast surface display-derived insights into manipulating this critical signaling axis may aid in the design of novel anti-resorptive therapies as well as provide a paradigm for design of other receptor-specific TNF superfamily ligand variants.
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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.