ArticleStem cells international2019
Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells.
Article in Stem cells international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Heterotopic Ossification: Molecular Drivers, Subtype-Specific Mechanisms, and Translational Therapeutic Advances.Biomolecules · 2026Review
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Hedgehog Signalling in Osteogenesis and Bone Metabolism: Molecular Mechanisms, Regulatory Networks and Implications for Skeletal Disease.Journal of cellular and molecular medicine · 2025Review
- Distinct ossification trade-offs illuminate the shoulder girdle reconfiguration at the water-to-land transition.Nature communications · 2025Article
- Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing.Current issues in molecular biology · 2025Article
- Heterotopic ossification: Current developments and emerging potential therapies.Chinese medical journal · 2025Review
- Role of hedgehog signaling in the pathogenesis and therapy of heterotopic ossification.Frontiers in cell and developmental biology · 2024Review
- Eradicating the tumor "seeds": nanomedicines-based therapies against cancer stem cells.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2023Review
- Inhibition of GSK-3β Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2.International journal of molecular sciences · 2023Article
- Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Zebrafish heart regeneration after coronary dysfunction-induced cardiac damage.Developmental biology · 2022Article
- GSK-3β suppression upregulates Gli1 to alleviate osteogenesis inhibition in titanium nanoparticle-induced osteolysis.Journal of nanobiotechnology · 2022Article
- On the horizon: Hedgehog signaling to heal broken bones.Bone research · 2022Review
- Hedgehog signaling underlying tendon and enthesis development and pathology.Matrix biology : journal of the International Society for Matrix Biology · 2022Review
- Cancer Stem Cell for Tumor Therapy.Cancers · 2021Review
- Tissue Engineering Strategies to Increase Osteochondral Regeneration of Stem Cells; a Close Look at Different Modalities.Stem cell reviews and reports · 2021Review
- Regulation of Osteoblast Differentiation by Cytokine Networks.International journal of molecular sciences · 2021Review
- MicroRNA-409-3p promotes osteoblastic differentiation via activation of Wnt/β-catenin signaling pathway by targeting SCAI.Bioscience reports · 2021Article
- JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells.Molecules (Basel, Switzerland) · 2021Article
- The Role of Smoothened in Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHedgehog (Hh) signaling is essential for osteoblast differentiation of mesenchymal progenitors during endochondral bone formation. However, the critical role of Hh signaling during adult bone remodeling remains to be elucidated.
methodsA Smoothened (SMO) antagonist/Hedgehog inhibitor, BMS-833923, identified during a functional screening of a stem cell signaling small molecule library, was investigated for its effects on the osteoblast differentiation of human skeletal (mesenchymal) stem cells (hMSC). Alkaline phosphatase (ALP) activity and Alizarin red staining were employed as markers for osteoblast differentiation and in vitro mineralization capacity, respectively. Global gene expression profiling was performed using the Agilent® microarray platform. Effects on in vivo ectopic bone formation were assessed by implanting hMSC mixed with hydroxyapatite-tricalcium phosphate granules subcutaneously in 8-week-old female nude mice, and the amount of bone formed was assessed using quantitative histology.
resultsBMS-833923, a SMO antagonist/Hedgehog inhibitor, exhibited significant inhibitory effects on osteoblast differentiation of hMSCs reflected by decreased ALP activity, in vitro mineralization, and downregulation of osteoblast-related gene expression. Similarly, we observed decreased in vivo ectopic bone formation. Global gene expression profiling of BMS-833923-treated compared to vehicle-treated control cells, identified 348 upregulated and 540 downregulated genes with significant effects on multiple signaling pathways, including GPCR, endochondral ossification, RANK-RANKL, insulin, TNF alpha, IL6, and inflammatory response. Further bioinformatic analysis employing Ingenuity Pathway Analysis revealed significant enrichment in BMS-833923-treated cells for a number of functional categories and networks involved in connective and skeletal tissue development and disorders, e.g., NF
conclusionsWe identified SMO/Hedgehog antagonist (BMS-833923) as a powerful inhibitor of osteoblastic differentiation of hMSC that may be useful as a therapeutic option for treating conditions associated with high heterotopic bone formation and mineralization.
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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.