ArticleThe Journal of biological chemistry2011
The Casitas B lineage lymphoma (Cbl) mutant G306E enhances osteogenic differentiation in human mesenchymal stromal cells in part by decreased Cbl-mediated platelet-derived growth factor receptor alpha and fibroblast growth factor receptor 2 ubiquitination.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 33 citations in OpenAlex.
- Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer.Molecular cancer · 2024Review
- CREG1 deficiency impaired myoblast differentiation and skeletal muscle regeneration.Journal of cachexia, sarcopenia and muscle · 2024Article
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- OTUB1 promotes osteoblastic bone formation through stabilizing FGFR2.Signal transduction and targeted therapy · 2023Article
- miR-338-3p acts as a tumor suppressor in lung squamous cell carcinoma by targetingCancer pathogenesis and therapy · 2023Article
- Stages of preadipocyte differentiation: biomarkers and pathways for extracellular structural remodeling.Hereditas · 2022Article
- Ubiquitin modification in osteogenic differentiation and bone formation: From mechanisms to clinical significance.Frontiers in cell and developmental biology · 2022Review
- All Good Things Must End: Termination of Receptor Tyrosine Kinase Signal.International journal of molecular sciences · 2021Review
- Review
- E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation.Frontiers in cell and developmental biology · 2021Review
- MiR-486-5p Suppresses Proliferation and Migration of Hepatocellular Carcinoma Cells through Downregulation of the E3 Ubiquitin Ligase CBL.BioMed research international · 2019Article
- Review
- Deubiquitinating Enzymes and Bone Remodeling.Stem cells international · 2018Review
- MicroRNA-155 regulates the proliferation, cell cycle, apoptosis and migration of colon cancer cells and targets CBL.Experimental and therapeutic medicine · 2017Article
- Article
- Fibroblast growth factor signaling in myofibroblasts differs from lipofibroblasts during alveolar septation in mice.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.Cellular and molecular life sciences : CMLS · 2015Review
- Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.PloS one · 2015Article
- Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.Bone · 2014Article
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Authors and funding
3 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Human bone marrow-derived mesenchymal stromal cells (hMSCs) have the capacity to differentiate into several cell types including osteoblasts and are therefore an important cell source for bone tissue regeneration. A crucial issue is to identify mechanisms that trigger hMSC osteoblast differentiation to promote osteogenic potential. Casitas B lineage lymphoma (Cbl) is an E3 ubiquitin ligase that ubiquitinates and targets several molecules for degradation. We hypothesized that attenuation of Cbl-mediated degradation of receptor tyrosine kinases (RTKs) may promote osteogenic differentiation in hMSCs. We show here that specific inhibition of Cbl interaction with RTKs using a Cbl mutant (G306E) promotes expression of osteoblast markers (Runx2, alkaline phosphatase, type 1 collagen, osteocalcin) and increases osteogenic differentiation in clonal bone marrow-derived hMSCs and primary hMSCs. Analysis of molecular mechanisms revealed that the Cbl mutant increased PDGF receptor α and FGF receptor 2 but not EGF receptor expression in hMSCs, resulting in increased ERK1/2 and PI3K signaling. Pharmacological inhibition of FGFR or PDGFR abrogated in vitro osteogenesis induced by the Cbl mutant. The data reveal that specific inhibition of Cbl interaction with RTKs promotes the osteogenic differentiation program in hMSCs in part by decreased Cbl-mediated PDGFRα and FGFR2 ubiquitination, providing a novel mechanistic approach targeting Cbl to promote the osteogenic capacity of hMSCs.
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