ArticleThe Journal of biological chemistry2010
Receptor activator of NF-{kappa}B (RANK) cytoplasmic IVVY535-538 motif plays an essential role in tumor necrosis factor-{alpha} (TNF)-mediated osteoclastogenesis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.International journal of molecular sciences · 2023Review
- Major vault protein (MVP) negatively regulates osteoclastogenesis via calcineurin-NFATc1 pathway inhibition.Theranostics · 2021Article
- The molecular mechanism of platelet lysate promotes transformation of non-union cells into osteoblasts.Translational cancer research · 2020Article
- Specific RANK Cytoplasmic Motifs Drive Osteoclastogenesis.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Article
- C/EBPα transcription factor is regulated by the RANK cytoplasmicThe Journal of biological chemistry · 2018Article
- Cyclophosphamide causes osteoporosis in C57BL/6 male mice: suppressive effects of cyclophosphamide on osteoblastogenesis and osteoclastogenesis.Oncotarget · 2017Article
- Cellular and Molecular Pathways Leading to External Root Resorption.Journal of dental research · 2017Review
- CSTB Downregulation Promotes Cell Proliferation and Migration and Suppresses Apoptosis in Gastric Cancer SGC-7901 Cell Line.Oncology research · 2016Article
- Interaction of Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) and Vav3 in the Receptor Activator of Nuclear Factor κB (RANK) Signaling Complex Enhances Osteoclastogenesis.The Journal of biological chemistry · 2016Article
- CCAAT/Enhancer-binding Protein α (C/EBPα) Is Important for Osteoclast Differentiation and Activity.The Journal of biological chemistry · 2016Article
- Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model.Acta histochemica et cytochemica · 2016Article
- Notch signaling promotes osteoclast maturation and resorptive activity.Journal of cellular biochemistry · 2015Article
- The IVVY Motif and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Sites in the Cytoplasmic Domain of the Receptor Activator of Nuclear Factor κB (RANK) Cooperate to Induce Osteoclastogenesis.The Journal of biological chemistry · 2015Article
- Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.Progress in molecular biology and translational science · 2015Review
- Molecular mechanism of thiazolidinedione-mediated inhibitory effects on osteoclastogenesis.PloS one · 2014Article
- Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process.Biochemical and biophysical research communications · 2013Article
- RNA interference-mediated silencing of Atp6i prevents both periapical bone erosion and inflammation in the mouse model of endodontic disease.Infection and immunity · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor necrosis factor-α (TNF) enhances osteoclast formation and activity leading to bone loss in various pathological conditions, but its precise role in osteoclastogenesis remains controversial. Although several groups showed that TNF can promote osteoclastogenesis independently of the receptor activator of NF-κB (RANK) ligand (RANKL), others demonstrated that TNF-mediated osteoclastogenesis needs permissive levels of RANKL. Here, we independently reveal that although TNF cannot stimulate osteoclastogenesis on bone slices, it can induce the formation of functional osteoclasts on bone slices in the presence of permissive levels of RANKL or from bone marrow macrophages (BMMs) pretreated by RANKL. TNF can still promote the formation of functional osteoclasts 2 days after transient RANKL pretreatment. These data have confirmed that TNF-mediated osteoclastogenesis requires priming of BMMs by RANKL. Moreover, we investigated the molecular mechanism underlying the dependence of TNF-mediated osteoclastogenesis on RANKL. RANK, the receptor for RANKL, contains an IVVY(535-538) motif that has been shown to play a vital role in osteoclastogenesis by committing BMMs to the osteoclast lineage. We show that TNF-induced osteoclastogenesis depends on RANKL to commit BMMs to the osteoclast lineage and RANKL regulates the lineage commitment through the IVVY motif. Mechanistically, the IVVY motif controls the lineage commitment by reprogramming osteoclast genes into an inducible state in which they can be activated by TNF. Our findings not only provide important mechanistic insights into the action of RANKL in TNF-mediated osteoclastogenesis but also establish that the IVVY motif may serve as an attractive therapeutic target for bone loss in various bone disorders.
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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.