ArticlePloS one2013
Characterization of the molecular mechanism of the bone-anabolic activity of carfilzomib in multiple myeloma.
Article in PloS one, 2013. 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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The trial behind it
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma.Hematological oncology · 2020Trial
- Pathophysiology and therapeutic advances in myeloma bone disease.Chronic diseases and translational medicine · 2022Review
- Myeloma Bone Disease: A Comprehensive Review.International journal of molecular sciences · 2021Review
- Article
- Efficacy and Safety of Balloon Kyphoplasty for Pathological Vertebral Fractures in Patients with Hematological Malignancies in Our Institution.Internal medicine (Tokyo, Japan) · 2021Article
- Article
- The role of Wnt/β-catenin signaling pathway in the pathogenesis and treatment of multiple myeloma (review).American journal of translational research · 2021Review
- 3D Printing of Tricalcium Phosphate/Poly Lactic-co-glycolic Acid Scaffolds Loaded with Carfilzomib for Treating Critical-sized Rabbit Radial Bone Defects.International journal of bioprinting · 2021Article
- The HGF/Met/NF-κB Pathway Regulates RANKL Expression in Osteoblasts and Bone Marrow Stromal Cells.International journal of molecular sciences · 2020Article
- Ixazomib Improves Bone Remodeling and Counteracts sonic Hedgehog signaling Inhibition Mediated by Myeloma Cells.Cancers · 2020Article
- MAFb protein confers intrinsic resistance to proteasome inhibitors in multiple myeloma.BMC cancer · 2018Article
- Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.Molecular biology of the cell · 2017Article
- Adipose, Bone, and Myeloma: Contributions from the Microenvironment.Calcified tissue international · 2017Review
- An Evidence-Based Approach to Myeloma Bone Disease.Current hematologic malignancy reports · 2017Review
- MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma.Blood · 2016Article
- Carfilzomib Triggers Cell Death in Chronic Lymphocytic Leukemia by Inducing Proapoptotic and Endoplasmic Reticulum Stress Responses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Review
- Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma.Targeted oncology · 2016Review
- Well plate-based perfusion culture device for tissue and tumor microenvironment replication.Lab on a chip · 2015Article
- The Proteasome Inhibitor Carfilzomib Suppresses Parathyroid Hormone-induced Osteoclastogenesis through a RANKL-mediated Signaling Pathway.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Carfilzomib, the next generation of proteasome inhibitor, may increase osteoblast-related markers in patients with multiple myeloma, but the molecular mechanism of its effect on mesenchymal stem cell differentiation to osteoblasts remains unknown. Herein, we demonstrated that carfilzomib significantly promoted mesenchymal stem cell differentiation into osteoblasts. In osteoprogenitor cells and primary mesenchymal stem cells from patients with myeloma, carfilzomib induced increases in alkaline phosphatase activity, matrix mineralization, and calcium deposition via Wnt-independent activation of β-catenin/TCF signaling. Using affinity pull-down assays with immunoblotting analysis and immunofluorescence, we found that carfilzomib induced stabilization of both free and active forms of β-catenin in a time- and dose-dependent manner that was not associated with β-catenin transcriptional regulation. Nuclear translocation of β-catenin protein was associated with TCF transcriptional activity that was independent of the effects of GSK3β-activation and of signaling induced by 19 Wnt ligands, 10 Frizzled receptors, and LRP5/6 co-receptors. Blocking activation of β-catenin/TCF signaling by dominant negative TCF1 or TCF4 attenuated carfilzomib-induced matrix mineralization. Thus, carfilzomib induced osteoblast differentiation via Wnt-independent activation of the β-catenin/TCF pathway. These results provide a novel molecular mechanism critical to understanding the anabolic role of carfilzomib on myeloma-induced bone disease.
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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.