ArticleStem cell research & therapy2025
Sildenafil promotes osteogenic differentiation of human mesenchymal stem cells and inhibits bone loss by affecting the TGF-β signaling pathway.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- IRF1 regulates apoptosis and osteogenic differentiation of bone marrow mesenchymal stem cells and ameliorates osteoporosis by activating the PI3K/AKT signaling pathway.Journal of advanced research · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- FZD6 mediates the contributing role of miR-199a-5p in the adipogenesis of bone marrow mesenchymal stem cells derived from aplastic anemia.Scientific reports · 2025Article
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10 authors.
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Abstract
backgroundOsteoporosis, a common bone disorder, is primarily managed pharmacologically. However, existing medications are associated with non-trivial side-effects. Sildenafil, which already finds many clinical applications, promotes angiogenesis and cellular differentiation. Osteoporotic patients often exhibit a reduced intraosseous vasculature and impaired cellular differentiation; sildenafil may thus usefully treat osteoporosis.
methodsHere, the effects of sildenafil on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) were explored, as were the molecular mechanisms in play. We treated hMSCs with varying concentrations of sildenafil and measured cell proliferation and osteogenic differentiation in vitro. We used a mouse model of subcutaneous ectopic osteogenesis to assess sildenafil's effect on hMSC osteogenic differentiation in vivo. We also explored the effects of sildenafil on bone loss in tail-suspended (TS) and ovariectomized (OVX) mice. Mechanistically, we employed RNA-sequencing to define potentially relevant molecular pathways.
resultsThe appropriate concentrations of sildenafil significantly enhanced osteogenic hMSC differentiation; the optimal sildenafil concentration may be 10 mg/L. Sildenafil mitigated osteoporosis in OVX and TS mice. The appropriate concentrations of sildenafil probably promoted hMSC osteogenic differentiation by acting on the transforming growth factor-β (TGF-β) signaling pathway.
conclusionsIn conclusion, sildenafil enhanced hMSC osteogenic differentiation and inhibited bone loss. Sildenafil may usefully treat osteoporosis. Our findings offer new insights into the physiological effects of the medicine.
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