ArticleMolecules and cells2011
Simvastatin promotes osteogenic differentiation of mouse embryonic stem cells via canonical Wnt/β-catenin signaling.
Article in Molecules and cells, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Silk-coated PLGA non-spherical microparticles for simvastatin delivery in rat maxillofacial bone regeneration.Regenerative biomaterials · 2026Article
- Osteogenic Potential of Simvastatin and Fluvastatin in an Organotypic Bone Model.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis.Biomedicines · 2025Article
- Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.Pharmacological reports : PR · 2025Review
- Evaluating Bioassays for the Determination of Simvastatin's Osteogenic Activity: A Systematic Review.Journal of functional biomaterials · 2025Review
- Association of higher potency statin use with risk of osteoporosis and fractures in patients with stroke in a Korean nationwide cohort study.Scientific reports · 2024Article
- The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and the risk of osteoporosis among U.S. adults: analysis of NHANES data.Lipids in health and disease · 2024Article
- Article
- Analysis of Why Alzheimer's Dementia Never Spontaneously Reverses, Suggests the Basis for Curative Treatment.Journal of clinical medicine · 2023Article
- Bioinspired sandwich-like hybrid surface functionalized scaffold capable of regulating osteogenesis, angiogenesis, and osteoclastogenesis for robust bone regeneration.Materials today. Bio · 2022Article
- Osteogenic Differentiation Effect of BMP-9 with Phenamil and Simvastatin on Intact Human Amniotic Epithelial Stem CellsIranian biomedical journal · 2022Article
- Molecular targets of statins and their potential side effects: Not all the glitter is gold.European journal of pharmacology · 2022Review
- Bone Health in Patients with Dyslipidemias: An Underestimated Aspect.International journal of molecular sciences · 2022Review
- Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia.NPJ aging and mechanisms of disease · 2021Article
- Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells.Biomedicines · 2021Article
- Adiponectin as Well as Compressive Forces RegulateFrontiers in cell and developmental biology · 2021Article
- ALK5 i II Accelerates Induction of Adipose-Derived Stem Cells toward Schwann Cells through a Non-Smad Signaling Pathway.Stem cells international · 2021Article
- Atorvastatin promotes bone formation in aged apoEJournal of orthopaedic surgery and research · 2020Article
- Enhanced osteogenesis and therapy of osteoporosis using simvastatin loaded hybrid system.Bioactive materials · 2020Article
- Annatto-Derived Tocotrienol Promotes Mineralization of MC3T3-E1 Cells by Enhancing BMP-2 Protein Expression via Inhibiting RhoA Activation and HMG-CoA Reductase Gene Expression.Drug design, development and therapy · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has been known to reduce cholesterol biosynthesis. However, recent studies demonstrate that simvastatin shows diverse cholesterol-independent functions including cellular differentiation. In this study, we investigated the stimulatory effect of simvastatin on the osteogenic differentiation of mouse embryonic stem cells (ESCs). The osteogenic effect of simvastatin was observed at relatively low doses (ranging from 1 nM to 200 nM). Incubation of ESCs in simvastatin-supplemented osteogenic medium significantly increased alkaline phosphatase (ALP) activity at day 7. The matrix mineralization was also augmented and demonstrated pivotal levels after 14 days incubation of simvastatin. Osteogenic differentiation of ESCs by simvastatin was determined by upregulation of the mRNA expression of runtrelated gene 2 (Runx2), osterix (OSX), and osteocalcin (OCN) as osteogenic transcription factors. Moreover, the increased protein expression of OCN, osteopontin (OPN), and collagen type I (Coll I) was assessed using Western blot analysis and immunocytochemistry. However, the blockage of canonical Wnt signaling by DKK-1 downregulated simvastatin-induced ALP activity and the mRNA expression of each osteogenic transcription factor. Furthermore, the β-catenin specific siRNA transfection decreased the protein levels of OCN, OPN, and Coll I. Collectively, these findings suggest that simvastatin enhances the differentiation of ESCs toward osteogenic lineage through activation of canonical Wnt/β-catenin signaling.
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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.