Simvastatin coating of TiO2 scaffold induces osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells

Pullisaar, Helen; Reseland, Janne Elin; Haugen, Håvard Jostein; Brinchmann, Jan E.; Østrup, Esben

doi:10.1016/j.bbrc.2014.03.133

Cited by 45 publications

(36 citation statements)

References 41 publications

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“…This result may have arisen from the relatively early time points we chose for detection, during which OCN expression is at a relatively low level and less sensitive to simvastatin stimulation. A previous in vitro study reported that simvastatin‐treated adipose tissue‐derived mesenchymal stem cells showed significant elevated expression of ALP and COL1, but not OCN, at 7 and 14 days . Moreover, another study reported similar results to our present finding, as periodontal ligament cells showed significant calcium accumulation at 21 days, but not 7 or 14 days after simvastatin stimulation .…”

Section: Discussionsupporting

confidence: 90%

Identification of Gli1‐interacting proteins during simvastatin‐stimulated osteogenic differentiation of bone marrow mesenchymal stem cells

Chi

Fan

et al. 2019

J of Cellular Biochemistry

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Simvastatin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Our study aimed to illuminate the underlying mechanism, with a specific focus on the role of Hedgehog signaling in this process. BMSCs cultured with or without 10−7 mol/L simvastatin were subjected to evaluation of osteogenic differentiation capacity. Osteogenic markers such as type 1 collagen (COL1) and osteocalcin (OCN), as well as key molecules of Hedgehog signaling molecules, were examined by Western blot and real‐time polymerase chain reaction (PCR). Co‐immunoprecipitation and mass spectrometry assays were applied to screen for Gli1‐interacting proteins. Cyclopamine (Cpn) was used as a Hedgehog signaling inhibitor. Our results indicated that simvastatin increased alkaline phosphatase (ALP) activity; mineralization of extracellular matrix; mRNA expression of ALP, COL1, and OCN; and expression and nuclear translocation of Gli1. Contrasting effects were observed in Cpn‐exposed groups, but were partially rescued by the simvastatin treatment. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that Gli1‐interacting proteins were primarily associated with mitogen‐activated protein kinase (MAPK) (P = 7.04E−04), hippo, insulin, and glucagon signaling. Further, hub genes identified by protein‐protein interaction network analysis included Gli1‐interacting proteins such as Ppp2r1a, Rac1, Etf1, and XPO1/CRM1. In summary, the current study showed that the mechanism by which simvastatin stimulates osteogenic differentiation of BMSCs involves activation of Hedgehog signaling, as indicated by interactions with Gli1 and, most notably, the MAPK signaling pathway.

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Section: Discussionsupporting

confidence: 90%

Identification of Gli1‐interacting proteins during simvastatin‐stimulated osteogenic differentiation of bone marrow mesenchymal stem cells

Chi

Fan

et al. 2019

J of Cellular Biochemistry

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“…This finding was corroborated by the other tests performed in this study, which evaluated levels of apoptosis of HDPCs and HPLFs by flow cytometry after Annexin V/propidium iodide double staining, actin cytoskeleton and nuclear morphology by phalloidin-FITC and 40,6-diamidino-2-phenylindole dihydrochloride staining, in which no cell structure damage was observed under these conditions. 29 Moreover, some researchers have demonstrated a decrease in cell viability mediated by SV for other types of cells, such as smooth muscle cells, 31 neuronal cells, 32 bone marrow stem cells (BMSC), 33 adipose derivate mesenchymal stem cells (AD-MSC) 34 and hDSPCs cells. 22 Okamoto et al 14 reported that when SV concentrations higher than 1 µM were applied to hDSPCs cells, they inhibited the formation of actin fibers and interfered with progression of the cell cycle regulated by the Rho pathway.…”

Section: Discussionmentioning

confidence: 99%

Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells

et al. 2017

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The aim of this study was to evaluate the bioactivity and cytocompatibility of simvastatin (SV) applied to MDPC-23 odontoblast-like cells. For this purpose, MDPC-23 cells were seeded in 96-well plates and submitted to treatments with 0.01 or 0.1 µM of SV for 24 h, 72 h or continuously throughout the experimental protocol. The negative control group (NC) was maintained in DMEM. Cell viability (MTT), ALP activity (thymolphthalein monophosphate), and mineralized matrix deposition (alizarin red) were analyzed at several time points. The data were submitted to ANOVA and Tukey's test (α = 0.05). Although cell viability was observed in the groups treated with SV, these groups did not differ from the NC up to 7 days. There was a reduction in cell viability for the groups treated with 0.1 µM of SV for 72 h, and submitted to continuous mode after 14 days. A significant increase in ALP activity occurred in the group treated with 0.01 µM of SV for 24 h, compared with the NC; however, only the group treated with 0.1 µM of SV in continuous mode reduced the ALP activity, in comparison with the NC. After 14 days, only continuous treatment with 0.1 µM of SV did not differ from NC, whereas the other experimental groups showed increased mineralized matrix deposition. Thus, it was concluded that low concentrations of simvastatin were bioactive and cytocompatible when applied for short periods to cultured MDPC-23 odontoblast-like cells.

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“…Another equally attractive synthetic drug currently utilized in bone tissue engineering which is able to mimic the effect of BMP-2 is simvastatin which has been shown to enhance bone formation in particular by promoting the differentiation of cells into the osteogenic lineage. This has been reported in a study by Pullisaar et al [14] where osteogenic differentiation was achieved in human adipose tissuederived mesenchymal stem cells due to the presence of simvastatin.…”

Section: Commonly Employed Drugs In Bone Tissue Engineeringmentioning

confidence: 56%

Bone Tissue Engineering Drug Delivery

Costa

2015

Curr Mol Bio Rep

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Tissue engineering shows the potential to address the growing demand for bone tissue substitutes resulting from trauma, disease, and ageing. The utilization of drugs in combination with tissue engineering strategies has resulted in a new generation of osteoinductive scaffolds which are able to improve the speed and quality of new bone formation. This review briefly describes some of the most recent and innovative advances resulting from the combination of drug delivery methodologies with tissue engineering strategies directed at the regeneration of bone tissue. It describes some of the most commonly utilized drugs as well as some of the strategies most commonly employed to accurately direct the delivery of drugs to specific sites and cells. This review also describes several strategies which enable controlled drug release in response to specific stimuli which can be provided by the surrounding environment or medically induced.

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Simvastatin coating of TiO2 scaffold induces osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells

Cited by 45 publications

References 41 publications

Identification of Gli1‐interacting proteins during simvastatin‐stimulated osteogenic differentiation of bone marrow mesenchymal stem cells

Identification of Gli1‐interacting proteins during simvastatin‐stimulated osteogenic differentiation of bone marrow mesenchymal stem cells

Biostimulatory effects of simvastatin on MDPC-23 odontoblast-like cells

Bone Tissue Engineering Drug Delivery

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