Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts
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RESEARCH
Open Access
Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts Martin Mariano Isabelo Sabandal1* , Edgar Schäfer1, Jonathan Aed1,2, Susanne Jung2, Johannes Kleinheinz2 and Sonja Sielker2
Abstract Background: Frequently statins were administered to reduce the LDL-concentration in circulating blood. Especially simvastatin (SV) is an often prescribed statin. Pleiotropic effects of these drugs were reported. Thus, the aim of this study was to evaluate effects of SV on osteoblastic mineralization. Methods: After informed consent primary osteoblasts were collected from tissue surplus after treatment of 14 individuals in the Department of Cranio-Maxillofacial Surgery, University Hospital Münster. The cells were passaged according to established protocols. Viability, mineralization capability and osteoblastic marker (alkaline phosphatase) were determined at day 9, 13 and 16 after adding various SV concentrations (0.05 μM, 0.1 μM, 0.5 μM, 1.0 μM). Statistical analysis was performed using the Kruskal-Wallis-test. Results: The cell cultures showed a time and dose-dependent significantly decreased viability (p < 0.01) and a significantly increased mineralization (p < 0.01) in a late mineralization stage after adding SV. The typical alteration of the alkaline phosphatase (ALP) levels during osteogenic differentiation was not recognizable. Conclusions: The pleiotropic effects found for different SV concentrations were possibly originated from other mineralization pathways beside the ALP induced one. Additionally, possible alterations of protein expression levels during mineralization and investigation of possible deviating application of SV in other treatment fields can be considered after gaining a deeper insight in the affected mechanisms. Keywords: Mineralization, Osteoblasts, Adverse effects, Simvastatin
Background The human bone is one of the highest mineralized tissues in human being. Although bone is highly mineralized a continuous remodelling of its structure depending on the physiological requirements is evident. The remodelling is balanced between osteoclasts which resorb bone and osteoblasts which build bone [1]. In between there are * Correspondence: [email protected] 1 Central Interdisciplinary Ambulance in the School of Dentistry, University of Münster, Albert-Schweitzer-Campus 1, Gebäude W30, Waldeyerstr. 30, 48149 Münster, Germany Full list of author information is available at the end of the article
osteocytes which are the formerly osteoblasts but embedded in surrounding bone. The function of the osteocytes alters with increasing age [2]. Due to the function and other evident complex growing patterns many different alterations can influence the formation of bone [3]. Several regularly administered pharmaceutics are known to exert an impact on bone remodelling and bone homeostasis [4, 5]. Bisphosphonates and denosumab are frequently used to treat different types of cancer [4] and osteoporosis [4, 5]. Both medicaments exert direct effects
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