ArticleClinical and translational medicine2021
A novel modified RANKL variant can prevent osteoporosis by acting as a vaccine and an inhibitor.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.International journal of surgery (London, England) · 2026Article
- Generation and Purification of RANKL-Derived Small-Fragment Variants for Osteoclast Inhibition.Pharmaceutics · 2025Article
- LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology.Biomedicines · 2025Review
- Role of endosomal RANKL-LGR4 signaling during osteoclast differentiation.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Advanced mutant receptor activator of nuclear factor kappa-Β ligand development with low affinity for osteoprotegerin.Clinical and translational medicine · 2025Article
- The role of LGR4 in bone metabolism and tumor bone metastasis.Frontiers in endocrinology · 2025Review
- Review
- An LGR4 agonist activates the GSK‑3β pathway to inhibit RANK‑RANKL signaling during osteoclastogenesis in bone marrow‑derived macrophages.International journal of molecular medicine · 2024Article
- Metabolic bone disorders and the promise of marine osteoactive compounds.Cellular and molecular life sciences : CMLS · 2023Review
- Molecular and Cellular Mechanisms of Osteoporosis.International journal of molecular sciences · 2023Review
- Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies.Biomedicines · 2023Review
- Urolithin B suppresses osteoclastogenesis via inhibiting RANKL-induced signalling pathways and attenuating ROS activities.Journal of cellular and molecular medicine · 2022Article
- Bone remodeling: an operational process ensuring survival and bone mechanical competence.Bone research · 2022Review
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- The "Three in One" Bone Repair Strategy for Osteoporotic Fractures.Frontiers in endocrinology · 2022Review
- Osteoporosis therapies and their mechanisms of action (Review).Experimental and therapeutic medicine · 2021Review
- A novel modified RANKL variant can prevent osteoporosis by acting as a vaccine and an inhibitor.Clinical and translational medicine · 2021Article
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe discovery of receptor activator of nuclear factor-ĸB ligand (RANKL) as the final effector in the pathogenesis of osteoporosis has led to a better understanding of bone remodeling. When RANKL binds to its receptor (RANK), osteoclastic differentiation and activation are initiated. Herein, we propose a strategy using a novel RANKL variant as a competitive inhibitor for RANKL. The RANKL variant activates LGR4 signaling, which competitively regulates RANK and acts as an immunogen that induces anti-RANKL antibody production.
methodsWe modified the RANK-binding site on RANKL using minimal amino acid changes in the RANKL complex and its counterpart receptor RANK and tried to evaluate the inhibitory effects on osteoclastogenesis.
resultsThe novel RANKL variant did not bind RANK in osteoclast progenitor cells, but activated LGR4 through the GSK3-β signaling pathway, thereby suppressing activated T cell cytoplasmic nuclear factor calcineurin-dependent 1 (NFATc1) expression and activity during osteoclastogenesis. Our RANKL variant generated high levels of RANKL-specific antibodies, blocked osteoclastogenesis, and inhibited osteoporosis in ovariectomized mouse models. Generated anti-RANKL antibodies showed a high inhibitory effect on osteoclastogenesis in vivo and in vitro.
conclusionsWe observed that the novel RANKL indeed blocks RANKL via LGR4 signaling and generates anti-RANKL antibodies, demonstrating an innovative strategy in the development of general immunotherapy.
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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.