ArticleJournal of materials science. Materials in medicine2019
20(S)-hydroxycholesterol and simvastatin synergistically enhance osteogenic differentiation of marrow stromal cells and bone regeneration by initiation of Raf/MEK/ERK signaling.
Article in Journal of materials science. Materials in medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Evaluating Bioassays for the Determination of Simvastatin's Osteogenic Activity: A Systematic Review.Journal of functional biomaterials · 2025Review
- MEK/ERK signaling drives the transdifferentiation of supporting cells into functional hair cells by modulating the Notch pathway.Stem cells translational medicine · 2024Article
- A Mendelian randomization study for drug repurposing reveals bezafibrate and fenofibric acid as potential osteoporosis treatments.Frontiers in pharmacology · 2023Article
- Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin.Clinical oral investigations · 2022Article
- Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status.Cells · 2021Review
- Effects of 20(S)-hydroxycholesterol on satellite cell proliferation and differentiation of broilers.Poultry science · 2021Article
- HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway.Stem cell research & therapy · 2020Article
- Oxysterols as promising small molecules for bone tissue engineering: Systematic review.World journal of orthopedics · 2020Article
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Authors and funding
6 authors.
Funding
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Abstract
Previous studies have demonstrated the significant roles of simvastatin (SVA) and oxysterols in the osteogenesis process. In this study, we evaluate the effect of a combination of SVA and 20(S)-hydroxycholesterol (20(S)OHC) on the cell viability and osteogenic differentiation of bone marrow stromal cells (BMSCs). After treatment with a control vehicle, SVA (0.025, 0.10, 0.25 or 1.0 μM), 20(S)OHC (5 μM), or a combination of both (0.25 μM SVA + 5 μM 20(S)OHC), the proliferation, apoptosis, ALP activity, mineralization, osteogenesis-related gene expression and Raf/MEK/ERK signaling activity in BMSCs were measured. Our results showed that high concentrations of SVA (0.25 and 1.0 μM) enhanced osteogenesis-related genes expression while attenuating cell viability. The addition of 5 μM 20(S)OHC induced significantly higher proliferative activity, which neutralized the inhibitory effect of SVA on the viability of BMSCs. Moreover, compared to supplementation with only one of the additives, combined supplementation with both SVA and 20(S)OHC induced significantly enhanced ALP activity, calcium sedimentation, osteogenesis-related genes (ALP, OCN and BMP-2) expression and Raf/MEK/ERK signaling activity in BMSCs; these enhancements were attenuated by treatment with the inhibitor U0126, indicating a significant role of Raf/MEK/ERK signaling in mediating the synergistically enhanced osteogenic differentiation of BMSCs by combined SVA and 20(S)OHC treatment. Additionally, histological examination confirmed a synergistic effect of SVA and 20(S)OHC on enhancing bone regeneration in a rabbit calvarial defect model. This newly developed SVA/20(S)OHC formulation may be used as an osteoinductive drug to enhance bone healing.
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