ArticleStem cell research & therapy2018
Stem cell library screen identified ruxolitinib as regulator of osteoblastic differentiation of human skeletal stem cells.
Article in Stem cell research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Dual Inhibition of GSK3 and JAK by BIO Suppresses Osteoblast Differentiation and Mineralization of Human Mesenchymal Cells.Current issues in molecular biology · 2026Article
- Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing.Current issues in molecular biology · 2025Article
- Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Inhibition of GSK-3β Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2.International journal of molecular sciences · 2023Article
- A novel decellularized matrix of Wnt signaling-activated osteocytes accelerates the repair of critical-sized parietal bone defects with osteoclastogenesis, angiogenesis, and neurogenesis.Bioactive materials · 2023Article
- Glycogen synthase kinase-3β inhibitor promotes the migration and osteogenic differentiation of rat dental pulp stem cells via the β-catenin/PI3K/Akt signaling pathway.Journal of dental sciences · 2022Article
- RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss.Cell regeneration (London, England) · 2021Article
- JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells.Molecules (Basel, Switzerland) · 2021Article
- Analysis of acute lymphoblastic leukemia drug sensitivity by changes in impedance via stromal cell adherence.PloS one · 2021Article
- The JAK1/STAT3/SOCS3 axis in bone development, physiology, and pathology.Experimental & molecular medicine · 2020Review
- Bioinformatics analysis of the biological changes involved in the osteogenic differentiation of human mesenchymal stem cells.Journal of cellular and molecular medicine · 2020Article
- MicroRNA-3148 acts as molecular switch promoting malignant transformation and adipocytic differentiation of immortalized human bone marrow stromal cells via direct targeting of the SMAD2/TGFβ pathway.Cell death discovery · 2020Article
- Notch Signaling Inhibition by LY411575 Attenuates Osteoblast Differentiation and Decreased Ectopic Bone Formation Capacity of Human Skeletal (Mesenchymal) Stem Cells.Stem cells international · 2019Article
- Hedgehog Signaling Inhibition by Smoothened Antagonist BMS-833923 Reduces Osteoblast Differentiation and Ectopic Bone Formation of Human Skeletal (Mesenchymal) Stem Cells.Stem cells international · 2019Article
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11 authors.
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Abstract
backgroundBetter understanding of the signaling pathways that regulate human bone marrow stromal stem cell (hBMSC) differentiation into bone-forming osteoblasts is crucial for their clinical use in regenerative medicine. Chemical biology approaches using small molecules targeting specific signaling pathways are increasingly employed to manipulate stem cell differentiation fate.
methodsWe employed alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin R staining to assess mineralized matrix formation of cultured hBMSCs. Changes in gene expression were assessed using an Agilent microarray platform, and data normalization and bioinformatics were performed using GeneSpring software. For in vivo ectopic bone formation experiments, hMSCs were mixed with hydroxyapatite-tricalcium phosphate granules and implanted subcutaneously into the dorsal surface of 8-week-old female nude mice. Hematoxylin and eosin staining and Sirius Red staining were used to detect bone formation in vivo.
resultsWe identified several compounds which inhibited osteoblastic differentiation of hMSCs. In particular, we identified ruxolitinib (INCB018424) (3 μM), an inhibitor of JAK-STAT signaling that inhibited osteoblastic differentiation and matrix mineralization of hMSCs in vitro and reduced ectopic bone formation in vivo. Global gene expression profiling of ruxolitinib-treated cells identified 847 upregulated and 822 downregulated mRNA transcripts, compared to vehicle-treated control cells. Bioinformatic analysis revealed differential regulation of multiple genetic pathways, including TGFβ and insulin signaling, endochondral ossification, and focal adhesion.
conclusionsWe identified ruxolitinib as an important regulator of osteoblast differentiation of hMSCs. It is plausible that inhibition of osteoblast differentiation by ruxolitinib may represent a novel therapeutic strategy for the treatment of pathological conditions caused by accelerated osteoblast differentiation and mineralization.
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