title: Simvastatin and zinc synergistically enhance osteoblasts activity and decrease the acute response of inflammatory cells.
abstract: Several ceramic biomaterials have been suggested as promising alternatives to autologous bone to replace or restore bone after trauma or disease. The osteoinductive potential of most scaffolds is often rather low by themselves and for this reason growth factors or drugs have been supplemented to these synthetic materials. Although some growth factors show good osteoinductive potential their drawback is their high cost and potential severe side effects. In this work the combination of the well-known drug simvastatin (SVA) and the inorganic element Zinc (Zn) is suggested as a potential additive to bone grafts in order to increase their bone regeneration/formation. MC3T3-E1 cells were cultured with Zn (10 and 25 µM) and SVA (0.25 and 0.4 µM) for 10 days to evaluate proliferation and differentiation, and for 22 days to evaluate secretion of calcium deposits. The combination of Zn (10 µM) and SVA (0.25 µM) significantly enhanced cell differentiation and mineralization in a synergetic manner. In addition, the release of reactive oxygen species (ROS) from primary human monocytes in contact with the same concentrations of Zn and SVA was evaluated by chemiluminescence. The combination of the additives decreased the release of ROS, although Zn and SVA separately caused opposite effects. This work shows that a new combination of additives can be used to increase the osteoinductive capacity of porous bioceramics.
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maryam
authors.initials: M
authors.lastname: Montazerolghaem
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden.|Science for Life Laboratory, Uppsala, Sweden.
authors.forename: Marjam
authors.initials: M
authors.lastname: Karlsson Ott
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden.|Science for Life Laboratory, Uppsala, Sweden.|Department Biomedical Engineering, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Tenje
authors.affiliation: Department Engineering Sciences, Uppsala University, Uppsala, Sweden. gemma.mestres@angstrom.uu.se.
authors.forename: Gemma
authors.initials: G
authors.lastname: Mestres
mesh_terms: D000210:Acute-Phase Reaction / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D019821:Simvastatin; D015032:Zinc