The functional mechanism of simvastatin in experimental osteoporosis

Dai, Lifen; Xu, Ming; Wu, Haiying; Xue, Lanjie; Yuan, Dekai; Wang, Yuan; Zhi-qiang, Shen; Zhao, Hongbin; Hu, Min

doi:10.1007/s00774-014-0638-y

Cited by 20 publications

(16 citation statements)

References 50 publications

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“…We here aimed to incorporate an osteostimulatory drug, simvastatin (SV), in a PLLA electrospun membrane and prolong its release, with the ultimate objective of creating a membrane with suitable biological properties for GBR applications. SV was chosen not only due to its well documented promotion of in vitro osteogenic differentiation 47,48 and bone regeneration, both in in vivo 49,50 and in clinical studies, 51 but also because it possesses a high thermal stability (T m of 139 C), and good solubility in organic solvents. 52,53 The effect of PLLA crystallinity on the release of SV was investigated.…”

Section: Discussionmentioning

confidence: 99%

Incorporation of simvastatin in PLLA membranes for guided bone regeneration: effect of thermal treatment on simvastatin release

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Incorporation of simvastatin in PLLA membranes for guided bone regeneration: effect of thermal treatment on simvastatin release

et al. 2018

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“…1,2 This class of drug can inhibit HMG-CoA reductase from turning into mevalonic acid, and is widely used for hyperlipidemia treatment. 1,2 Several researchers have demonstrated that SV has pleiotropic effects, including anti-inflammatory action, 2,3 induces angiogenesis and improves the function of endothelial cells, 4,5,6,7,8 as well as enhancing the synthesis and mineralization of bone 9,10,11,12,13 and dentin 6,14,15,16,17 matrices. The pathway for SV mediating osteo/odontogenic differentiation is not fully known.…”

Section: Introductionmentioning

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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“…Indeed, both in vitro and in vivo studies have reported the beneficial effects of statins on osteoblast differentiation and mineralization . Additionally, in vivo studies showed that statins are a potential treatment for osteoporosis . Based on these studies, we expected to find improved MSC‐derived osteoblast differentiation and/or mineralization and we speculated that SIM may antagonize the negative effects of HCQ.…”

Section: Discussionmentioning

confidence: 94%

Hydroxychloroquine decreases human MSC‐derived osteoblast differentiation and mineralization in vitro

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Peppel

Zillikens

et al. 2017

J Cellular Molecular Medi

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We recently showed that patients with primary Sjögren Syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favourable effects on BMD. To study the direct effects of HCQ on human MSC‐derived osteoblast activity. Osteoblasts were cultured from human mesenchymal stromal cells (hMSCs). Cultures were treated with different HCQ doses (control, 1 and 5 µg/ml). Alkaline phosphatase activity and calcium measurements were performed to evaluate osteoblast differentiation and activity, respectively. Detailed microarray analysis was performed in 5 µg/ml HCQ‐treated cells and controls followed by qPCR validation. Additional cultures were performed using the cholesterol synthesis inhibitor simvastatin (SIM) to evaluate a potential mechanism of action. We showed that HCQ inhibits both MSC‐derived osteoblast differentiation and mineralization in vitro. Microarray analysis and additional PCR validation revealed a highly significant up‐regulation of the cholesterol biosynthesis, lysosomal and extracellular matrix pathways in the 5 µg/ml HCQ‐treated cells compared to controls. Besides, we demonstrated that 1 µM SIM also decreases MSC‐derived osteoblast differentiation and mineralization compared to controls. It appears that the positive effect of HCQ on BMD cannot be explained by a stimulating effect on the MSC‐derived osteoblast. The discrepancy between high BMD and decreased MSC‐derived osteoblast function due to HCQ treatment might be caused by systemic factors that stimulate bone formation and/or local factors that reduce bone resorption, which is lacking in cell cultures.

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The functional mechanism of simvastatin in experimental osteoporosis

Cited by 20 publications

References 50 publications

Incorporation of simvastatin in PLLA membranes for guided bone regeneration: effect of thermal treatment on simvastatin release

Incorporation of simvastatin in PLLA membranes for guided bone regeneration: effect of thermal treatment on simvastatin release

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

Hydroxychloroquine decreases human MSC‐derived osteoblast differentiation and mineralization in vitro

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