ArticleCancers2020
The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Multifactorial Regulation of Inflammatory Bone Loss in Chronic Inflammatory and Immune-Associated Disorders: Osteoimmune Mechanisms and Translational Prospects of Natural Small Molecules.Calcified tissue international · 2026Review
- Repurposing Hetrombopag for Multiple Myeloma by Targeting PNPO: A Celastrol-Inspired Approach.Basic & clinical pharmacology & toxicology · 2026Article
- Brain-bone axis dysregulation: Biological code underlying the bidirectional association between depression and musculoskeletal disorders.Journal of orthopaedic translation · 2026Review
- Oxidative stress and antioxidant pathways in the pathogenesis of periodontitis and peri-implantitis: mechanistic insights and therapeutic potentials.Frontiers in oral health · 2026Review
- Nanozymes for Bone Regeneration: Mechanistic Insights into Immune and Metabolic Microenvironment Modulation.International journal of nanomedicine · 2026Review
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- Enhancing bone regeneration using kaempferol as an osteoprotective compound: signaling mechanisms, delivery strategies, and potential applications.Journal of biological engineering · 2025Review
- Management of hypertension addressing hyperuricaemia: introduction of nano-based approaches.Annals of medicine · 2024Review
- Curcumin-loaded scaffolds in bone regeneration.Heliyon · 2024Review
- Osteogenic mechanism of chlorogenic acid and its application in clinical practice.Frontiers in pharmacology · 2024Review
- Europium-Containing Nanospheres for Treating Ovariectomy-Induced Osteoporosis: Targeted Bone Remodeling and Macrophage Polarization Modulation.International journal of nanomedicine · 2024Article
- Mechanisms of preferential bone formation in myeloma bone lesions by proteasome inhibitors.International journal of hematology · 2023Article
- Article
- Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs.International journal of molecular sciences · 2023Review
- The Ethanol Extracts ofPlants (Basel, Switzerland) · 2023Article
- The Xanthine Oxidase Inhibitor Febuxostat Suppresses Adipogenesis and Activates Nrf2.Antioxidants (Basel, Switzerland) · 2023Article
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides.International journal of molecular sciences · 2022Article
- Gut microbiota modulates osteoclast glutathione synthesis and mitochondrial biogenesis in mice subjected to ovariectomy.Cell proliferation · 2022Article
- Underlying the Mechanisms of Doxorubicin-Induced Acute Cardiotoxicity: Oxidative Stress and Cell Death.International journal of biological sciences · 2022Review
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
Abstract
Receptor activator of NF-κB ligand (RANKL), a critical mediator of osteoclastogenesis, is upregulated in multiple myeloma (MM). The xanthine oxidase inhibitor febuxostat, clinically used for prevention of tumor lysis syndrome, has been demonstrated to effectively inhibit not only the generation of uric acid but also the formation of reactive oxygen species (ROS). ROS has been demonstrated to mediate RANKL-mediated osteoclastogenesis. In the present study, we therefore explored the role of cancer-treatment-induced ROS in RANKL-mediated osteoclastogenesis and the suppressive effects of febuxostat on ROS generation and osteoclastogenesis. RANKL dose-dependently induced ROS production in RAW264.7 preosteoclastic cells; however, febuxostat inhibited the RANKL-induced ROS production and osteoclast (OC) formation. Interestingly, doxorubicin (Dox) further enhanced RANKL-induced osteoclastogenesis through upregulation of ROS production, which was mostly abolished by addition of febuxostat. Febuxostat also inhibited osteoclastogenesis enhanced in cocultures of bone marrow cells with MM cells. Importantly, febuxostat rather suppressed MM cell viability and did not compromise Dox's anti-MM activity. In addition, febuxostat was able to alleviate pathological osteoclastic activity and bone loss in ovariectomized mice. Collectively, these results suggest that excessive ROS production by aberrant RANKL overexpression and/or anticancer treatment disadvantageously impacts bone, and that febuxostat can prevent the ROS-mediated osteoclastic bone damage.
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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.