Simvastatin exerts antiproliferative and differentiating effects on MG63 osteoblast‐like cells: Morphological and immunocytochemical study

Abstract

Background and Objective: Current evidence suggests that statins exert an anabolic effect on bone and may therefore impact on osteogenic differentiation and proliferation. These effects can be useful for their use in guided bone regeneration. The objective of this study was to determine the in vitro effects of simvastatin on the differentiation and proliferation of MG63 human osteoblast tumor cells. that may be useful against infections associated with bone healing. Experimental studies of implants in rodents found that simvastatin administration improved the bone contact ratio, bone density and osseointegration, 10,11 which was also found to be enhanced by topical fluvastatin application around implants. 12 In contrast, other authors found no increase in bone density in statin-treated defects, 13 and a recent study reported that simvastatin loading of implant surfaces exerted significant effects for only 2 weeks. 14 Formation of new bone tissue was observed in calvaria of rats after the topical injection of fluvastatin using tricalcium phosphate as carrier. 15 However, high doses of local statin can cause inflammation when used for bone regeneration, as reported by two studies in which simvastatin was applied to calvarial defects in rodents. 13,16 Simvastatin was found to affect osteogenic differentiation in a murine model, 17 while an in vitro study showed that exposure to this drug slightly increased osteoblast expression of osteocalcin, osteoprotegerin, alkaline phosphatase and other bone markers. Material and Methods 18The objective of the present study was to determine the in vitro effects of simvastatin on the differentiation and proliferation of the MG63 human tumor osteoblast cell line. | MATERIAL AND METHODSAll procedures in this study were performed in accordance with the 1964 Helsinki declaration and its later amendments. The study was approved by the Ethics Committee of the School of Dentistry of the University of Granada (reference: FOD/UGR/08/2016). | Cell line | MaterialsSimvastatin and dimethyl sulfoxide (DMSO) were obtained from Sigma-Aldrich LLC (St. Louis, MO, USA). Simvastatin was resuspended at a concentration of 20 mg/mL in DMSO and stored at −20°C. | Proliferation assayAfter

Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts

“…Additionally, osteoblastic differentiation and proliferation were evaluated [16,20,31]. The studies investigating the above mentioned parameters were performed using human cells of different tissues like bone marrow cells and mesenchymal stem cells [20], periodontal ligament cells (PDL-cells) [17,18,31], cells from adipose tissues [13,14], lung fibroblasts [19], immortalized multiple myeloma cells [15], osteoblast-like cell lines MG63 [30] and osteoblasts from bone chips [16].…”

“…The corresponding systemic available concentration of SV ranges due to the biological availability of 5% from 0.05 to 5 μM. The SV concentrations used in the current study were chosen based on the performed cytotoxicity test and correlated with those (0.001 μM up to 10 μM) used in previous studies using human cells [ 13 – 18 , 20 , 29 , 30 ]. Especially alterations of mineralization [ 14 , 31 ], osteogenic markers like ALP, OC, receptor activator of nuclear factor kappa-Β ligand, bone morphogenetic protein 2, bone sialoprotein and osteoprotegerin [ 18 , 20 , 31 ] were investigated previously.…”

Expression of Musashi-1 During Osteogenic Differentiation of Oral MSC: An In Vitro Study

“…In contrast, it has been assumed that as cells differentiate, MSI1 expression would decrease [21]. For example, our group has identified a decrease in MSI1 expression with osteogenic differentiation when stimulated by Simvastatin on osteoblast-like cells [22]. It must be mentioned, however, that some of these studies were not conducted on primary undifferentiated cells but on immortalized tumor-derived cell lines, such as MG-63.…”

A simvastatin-releasing scaffold with periodontal ligament stem cell sheets for periodontal regeneration

“…24 The cytotoxicity of high-dose SIM (> 0.1 μM ) has been reported in other studies. 1,8 PCL is a clinical-grade product, which would facilitate future transplantation. 15,27,28 When cultured on scaffolds in osteogenic medium for 21 days, PDLSCs formed abundant mineralized nodules.…”

“…Statins, the commonly prescribed cholesterol-lowering drugs in patients with hypercholesterolemia, have been shown to possess anti-inflammatory, antioxidant, and bone anabolic effects. [1][2][3] Simvastatin (SIM), at a low dose, is believed to facilitate periodontal hard tissue engineering by having an osteogenic effect in periodontal ligament stem cells (PDLSCs). 4 Multiple local applications of SIM are capable of strongly decreasing the amount of inflammation and bone loss in an experimental periodontitis rat model.…”