ArticleCancers2020
Ixazomib Improves Bone Remodeling and Counteracts sonic Hedgehog signaling Inhibition Mediated by Myeloma Cells.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Continuous multi-omics pathway enrichment analysis resolves hidden functional heterogeneity.Briefings in bioinformatics · 2026Article
- Bone-modifying therapy in multiple myeloma: a comprehensive review.Frontiers in oncology · 2026Review
- Breaking Barriers: The Role of the Bone Marrow Microenvironment in Multiple Myeloma Progression.International journal of molecular sciences · 2025Review
- Bone Effects of Anti-Cancer Treatments in 2024.Calcified tissue international · 2025Review
- Dendritic cells in multiple myeloma: from immune evasion to therapeutic potential.Frontiers in immunology · 2025Review
- Review
- Deubiquitinase USP17 Regulates Osteoblast Differentiation by Increasing Osterix Protein Stability.International journal of molecular sciences · 2023Article
- IGFBP-6 Alters Mesenchymal Stromal Cell Phenotype Driving Dasatinib Resistance in Chronic Myeloid Leukemia.Life (Basel, Switzerland) · 2023Article
- Mesenchymal stromal cells in tumor microenvironment remodeling of BCR-ABL negative myeloproliferative diseases.Frontiers in oncology · 2023Review
- Connexins Signatures of the Neurovascular Unit and Their Physio-Pathological Functions.International journal of molecular sciences · 2022Review
- Neuroprotective Role of α-Lipoic Acid in Iron-Overload-Mediated Toxicity and Inflammation in In Vitro and In Vivo Models.Antioxidants (Basel, Switzerland) · 2022Article
- Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain.International journal of molecular sciences · 2022Article
- Mechanism of Targeting the Hedgehog Signaling Pathway against Chemotherapeutic Resistance in Multiple Myeloma.Journal of oncology · 2022Article
- Article
- Research progress in proteasome inhibitor resistance to multiple myeloma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities.Cancers · 2021Review
- Article
- Review
- Focus on Osteosclerotic Progression in Primary Myelofibrosis.Biomolecules · 2021Review
- Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of plasma cells (PC) in the bone marrow (BM), leading to bone loss and BM failure. Osteolytic bone disease is a common manifestation observed in MM patients and represents the most severe cause of morbidity, leading to progressive skeletal damage and disabilities. Pathogenetic mechanisms of MM bone disease are closely linked to PCs and osteoclast (OCs) hyperactivity, coupled with defective osteoblasts (OBs) function that is unable to counteract bone resorption. The aim of the present study was to investigate the effects of Ixazomib, a third-generation proteasome inhibitor, on osteoclastogenesis and osteogenic differentiation. We found that Ixazomib was able to reduce differentiation of human monocytes into OCs and to inhibit the expression of OC markers when added to the OC medium. Concurrently, Ixazomib was able to stimulate osteogenic differentiation of human mesenchymal stromal cells (MSCs), increasing osteogenic markers, either alone or in combination with the osteogenic medium. Given the key role of Sonic Hedgehog (SHH) signaling in bone homeostasis, we further investigated Ixazomib-induced SHH pathway activation. This set of experiments showed that Ixazomib, but not Bortezomib, was able to bind the Smoothened (SMO) receptor leading to nuclear translocation of GLI1 in human MSCs. Moreover, we demonstrated that PCs act as GLI1 suppressors on MSCs, thus reducing the potential of MSCs to differentiate in OBs. In conclusion, our data demonstrated that Ixazomib regulates bone remodeling by decreasing osteoclastogenesis and prompting osteoblast differentiation via the canonical SHH signaling pathway activation, thus, representing a promising therapeutic option to improve the complex pathological condition of MM patients.
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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.