Effects on mineralisation potential of humane osteoblasts induced by simvastatin

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Abstract

Introduction Simvastatin (SV) is a member of the statin family. As a HMG-CoA reductase inhibitor, it is principal therapeutic agents in lowering blood cholesterol. Many pleiotropic effects are reported with SV. It showed e.g. anti-inflammatory effects and stimulated angiogenesis. Proven by animal experiments SV promotes osteoblast proliferation and differentiation, and suppressed osteoclasts. Methods In cell culture studies effects of SV on 6 primary mandibular osteoblast cell lines was analysed. A SV concentration of 0.01 up to 20 µM was used. A common clinically applied dosage of 5-40 mg/d matches with a systemic SV concentration of 0.05 - 5.0 µM. Analysed were effects on cell proliferation (MTT), vitality (living/dead staining), and cytotoxic effects (LDH). Further, effects on osteogenic activity (ALP) and mineralisation rate (alizarin red S quantification) were analysed. Statistical analysis was carried out by one way ANOVA and p<0.05 (SPSS; version 24). Results A SV concentration of > 1.0 µM was cytotoxic confirmed by decreased proliferation rate and living/dead staining. A dosage of 1 µM showed minor cytotoxic effects. The proliferation rate was weak compared to downgrading SV concentrations. Nevertheless cells survived and showed strong mineralisation rates. A SV dosage of 0.5 µM dependent earlier start of mineralisation accompanied with a higher mineralisation rate was observed. Conclusion SV enhanced mineralisation potential of mandibular primary osteoblast. And this stimulation occurs within common clinical applied dosages. This stimulation may have negative effects elicited by a possible unintentionally bone mineralisation. But on the other hand SV could be used as a stimulator for bone remineralisation.

Speakers from the University of Münster

Jung, Susanne	Clinic for Cranio-Maxillofacial Surgery
Kleinheinz, Johannes	Clinic for Cranio-Maxillofacial Surgery
Sabandal, Martin	Department of Operative and Preventive Dentistry
Schäfer, Edgar	Department of Operative and Preventive Dentistry
Sielker, Sonja	Clinic for Cranio-Maxillofacial Surgery