ArticleThe Journal of clinical investigation2015
Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Fabry Disease Associated With Myelodysplastic Syndrome: Case Report.Clinical case reports · 2025Article
- Adipose Tissue-Derived Mediators in Multiple Myeloma: Linking Obesity to Bone Disease via Inflammatory Pathways.International journal of molecular sciences · 2025Review
- Regulation of Glycosylation in Bone Metabolism.International journal of molecular sciences · 2024Review
- Article
- Lipid metabolic vulnerabilities of multiple myeloma.Clinical and experimental medicine · 2023Review
- Bone marrow adipocytes alteration in anMolecular genetics and metabolism reports · 2023Article
- Glucosylceramide Synthase Inhibitors Induce Ceramide Accumulation and Sensitize H3K27 Mutant Diffuse Midline Glioma to Irradiation.International journal of molecular sciences · 2023Article
- Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.Nature communications · 2022Article
- Crosstalk between dihydroceramides produced by Porphyromonas gingivalis and host lysosomal cathepsin B in the promotion of osteoclastogenesis.Journal of cellular and molecular medicine · 2022Article
- Role of Sphingolipids in Multiple Myeloma Progression, Drug Resistance, and Their Potential as Therapeutic Targets.Frontiers in oncology · 2022Review
- Iminosugar Glucosidase Inhibitors Reduce Hepatic Inflammation in Hepatitis A Virus-InfectedJournal of virology · 2021Article
- Gaucher disease: Basic and translational science needs for more complete therapy and management.Molecular genetics and metabolism · 2021Review
- Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density.Clinical nutrition (Edinburgh, Scotland) · 2021Article
- Screening of the small molecule library of Meinox enables the identification of anticancer compounds in pathologically distinct cancers.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Gb3-cSrc complex in glycosphingolipid-enriched microdomains contributes to the expression of p53 mutant protein and cancer drug resistance via β-catenin-activated RNA methylation.FASEB bioAdvances · 2020Article
- Review
- Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells.Experimental gerontology · 2020Article
- Immunoporosis: A New Role for Invariant Natural Killer T (NKT) Cells Through Overexpression of Nuclear Factor-κB Ligand (RANKL).Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts.Cancers · 2019Article
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
Abstract
Glycosphingolipids (GSLs) are essential constituents of cell membranes and lipid rafts and can modulate signal transduction events. The contribution of GSLs in osteoclast (OC) activation and osteolytic bone diseases in malignancies such as the plasma cell dyscrasia multiple myeloma (MM) is not known. Here, we tested the hypothesis that pathological activation of OCs in MM requires de novo GSL synthesis and is further enhanced by myeloma cell-derived GSLs. Glucosylceramide synthase (GCS) inhibitors, including the clinically approved agent N-butyl-deoxynojirimycin (NB-DNJ), prevented OC development and activation by disrupting RANKL-induced localization of TRAF6 and c-SRC into lipid rafts and preventing nuclear accumulation of transcriptional activator NFATc1. GM3 was the prevailing GSL produced by patient-derived myeloma cells and MM cell lines, and exogenous addition of GM3 synergistically enhanced the ability of the pro-osteoclastogenic factors RANKL and insulin-like growth factor 1 (IGF-1) to induce osteoclastogenesis in precursors. In WT mice, administration of GM3 increased OC numbers and activity, an effect that was reversed by treatment with NB-DNJ. In a murine MM model, treatment with NB-DNJ markedly improved osteolytic bone disease symptoms. Together, these data demonstrate that both tumor-derived and de novo synthesized GSLs influence osteoclastogenesis and suggest that NB-DNJ may reduce pathological OC activation and bone destruction associated with MM.
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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.