ArticleInternational journal of molecular sciences2021
Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- miR-326 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by targeting NAT10.Journal of orthopaedic surgery and research · 2026Article
- RANKL-convergent osteoimmune network framework in osteoporosis: integrating macrophage activation, T-cell imbalance, and cytokine crosstalk.Frontiers in immunology · 2026Review
- 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
- The role of LGR4 in bone metabolism and tumor bone metastasis.Frontiers in endocrinology · 2025Review
- Advanced mutant receptor activator of nuclear factor kappa-Β ligand development with low affinity for osteoprotegerin.Clinical and translational medicine · 2025Article
- Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.Molecular medicine (Cambridge, Mass.) · 2024Review
- 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
- Identification of recurrent variants implicated in disease in bicuspid aortic valve patients through whole-exome sequencing.Human genomics · 2022Article
- Osteoporosis pathogenesis and treatment: existing and emerging avenues.Cellular & molecular biology letters · 2022Review
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- Vericiguat Modulates Osteoclast Differentiation and Bone Resorption via a Balance between VASP and NF-Mediators of inflammation · 2022Article
- Osteoporosis therapies and their mechanisms of action (Review).Experimental and therapeutic medicine · 2021Review
- Osteoporosis: From Molecular Mechanisms to Therapies 3.0.International journal of molecular sciences · 2021Article
- The Effect of Acknowledged and Novel Anti-Rheumatic Therapies on Periodontal Tissues-A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRecently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK-RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model.
resultsAs a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.
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Registered trials
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