ArticleBMC cancer2010
The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts.
Article in BMC cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 78 citations in OpenAlex.
- A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients.Investigational new drugs · 2014Trial
- Vascular Endothelial cell-derived Exosomal miR-5p-13348_267 Regulates the Fate Determination of Bone Marrow Mesenchymal Stem Cells (BMSCs).Cell biochemistry and biophysics · 2026Article
- GATRSyn: Advancing Anticancer Drug Synergy Prediction Through Graph Attention Networks and Transformer-based Feature Re-embedding.Interdisciplinary sciences, computational life sciences · 2026Article
- Fueling bone loss: the immunometabolic reprogramming of the bone microenvironment in diabetic osteoporosis.Frontiers in immunology · 2026Review
- The Role of Senolytics in Osteoporosis.Biomolecules · 2025Review
- Inhibition of CD45-specific phosphatase activity restores the differentiation potential of aged mesenchymal stromal cells: implications in regenerative medicine.Biological research · 2025Article
- Bone Mineral Density, C-Terminal Telopeptide of Type I Collagen, and Osteocalcin as Monitoring Parameters of Bone Remodeling in CML Patients Undergoing Imatinib Therapy: A Basic Science and Clinical Review.Diseases (Basel, Switzerland) · 2024Review
- Role of the GRP78-c-Src signaling pathway on osteoblast differentiation of periodontal ligament fibroblasts induced by cyclic mechanical stretch.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2024Article
- Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation.Journal of orthopaedic translation · 2024Article
- Dasatinib-Triggered Severe Hypocalcemia in a Patient with Chronic Kidney Disease and Osteoporosis.Cureus · 2023Article
- RANKLInternational journal of oral science · 2023Article
- Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals.International journal of medical sciences · 2023Article
- In Situ-Forming Collagen/poly-γ-glutamic Acid Hydrogel System with Mesenchymal Stem Cells and Bone Morphogenetic Protein-2 for Bone Tissue Regeneration in a Mouse Calvarial Bone Defect Model.Tissue engineering and regenerative medicine · 2022Article
- Tyrosine Kinase Src Is a Regulatory Factor of Bone Homeostasis.International journal of molecular sciences · 2022Review
- Macrophages at the nexus of mesenchymal stromal cell potency: The emerging role of chemokine cooperativity.Stem cells (Dayton, Ohio) · 2021Review
- Bone marrow niches in the regulation of bone metastasis.British journal of cancer · 2021Review
- Mesenchymal stromal cell variables influencing clinical potency: the impact of viability, fitness, route of administration and host predisposition.Cytotherapy · 2021Article
- Bone Metastasis: Find Your Niche and Fit in.Trends in cancer · 2019Review
- Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators.Scientific reports · 2018Article
- Neuroprotective Effect of CeONeurochemical research · 2018Article
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7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.
methodsWe evaluated the effects of dasatinib on bone marrow-derived mesenchymal stromal cells (MSC) differentiation into osteoblasts, in the presence or absence of a mixture of dexamethasone, ascorbic acid and beta-glycerophosphate (DAG) for up to 21 days. The differentiation kinetics was assessed by evaluating mineralization of the extracellular matrix, alkaline phosphatase (ALP) activity, and expression of osteoblastic markers (receptor activator of nuclear factor kappa B ligand [RANKL], bone sialoprotein [BSP], osteopontin [OPN]).
resultsDasatinib significantly increased the activity of ALP and the level of calcium deposition in MSC cultured with DAG after, respectively, 7 and 14 days; it upregulated the expression of BSP and OPN genes independently of DAG; and it markedly downregulated the expression of RANKL gene and protein (decrease in RANKL/OPG ratio), the key factor that stimulates osteoclast differentiation and activity.
conclusionsOur results suggest a dual role for dasatinib in both (i) stimulating osteoblast differentiation leading to a direct increase in bone formation, and (ii) downregulating RANKL synthesis by osteoblasts leading to an indirect inhibition of osteoclastogenesis. Thus, dasatinib is a potentially interesting candidate drug for the treatment of osteolysis through its dual effect on bone metabolism.
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