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      Differential apoptotic response of MC3T3-E1 pre-osteoblasts to biodegradable magnesium alloys in an in vitro direct culture model

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          Abstract

          Abstract

          The biodegradable magnesium-based implants have been widely utilized in medical orthopedic applications in recent years. We have recently shown that direct culture on Pure Mg and Mg2Ag alloys lead to a progressive differentiation impairment of MC3T3-E1 pre-osteoblasts. In this study, we aimed to analyze the apoptotic reaction of MC3T3-E1 cells in response to the direct culture on Pure Mg, Mg2Ag and Extreme High Pure Mg (XHP Mg) alloy samples. Our results demonstrated that long-term culturing of MC3T3-E1 cells on Pure Mg and Mg2Ag alloys induce time-dependent expression of active caspase-3 (active casp-3) and cleaved PARP-1 (cl. PARP-1), the hallmark of apoptosis reactions concomitant with a significant increase in the number of dead cells. However, direct culture on XHP Mg material results in a lower number of dead cells in comparison to Pure Mg and Mg2Ag alloys. Furthermore, XHP Mg materials influence expression of apoptotic markers in a process resembles that of observed in osteogenic condition apparently indicative of MC3T3-E1 osteodifferentiation. This study indicates that Mg alloy samples mediated differential apoptotic reactions of MC3T3-E1 cells can be ascribed to factors such as distinct topography and hydrophobicity features of Mg material surfaces, contrasting nature/composition of corrosion products as well as different impurities of these materials. Therefore, initial Mg alloys surface preparation, controlling the growth and composition of corrosion products and Mg alloys purity enhancement are necessary steps towards optimizing the Mg alloys usage in medical orthopedic applications.

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          Most cited references29

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          Apoptosis: a review of programmed cell death.

          The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
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            Magnesium and its alloys as orthopedic biomaterials: a review.

            As a lightweight metal with mechanical properties similar to natural bone, a natural ionic presence with significant functional roles in biological systems, and in vivo degradation via corrosion in the electrolytic environment of the body, magnesium-based implants have the potential to serve as biocompatible, osteoconductive, degradable implants for load-bearing applications. This review explores the properties, biological performance, challenges and future directions of magnesium-based biomaterials.
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              The biochemistry of apoptosis.

              Apoptosis--the regulated destruction of a cell--is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cell's likelihood of activating its self-destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.
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                Author and article information

                Contributors
                +43 316 38572909 , ehsan.bonyadirad@medunigraz.at
                Journal
                J Mater Sci Mater Med
                J Mater Sci Mater Med
                Journal of Materials Science. Materials in Medicine
                Springer US (New York )
                0957-4530
                1573-4838
                5 September 2017
                5 September 2017
                2017
                : 28
                : 10
                : 155
                Affiliations
                [1 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Department of Orthopedics and Trauma Surgery, , Medical University Graz, ; Graz, Austria
                [2 ]ISNI 0000 0001 1033 9225, GRID grid.181790.6, Department of Polymer Engineering and Science, , Montanuniversitaet Leoben, ; Leoben, Austria
                [3 ]ISNI 0000 0001 2331 3059, GRID grid.7354.5, EMPA, Swiss Federal Laboratories for Materials Science and Technology, ; Duebendorf, Switzerland
                [4 ]ISNI 0000 0004 0541 3699, GRID grid.24999.3f, Institute of Materials Research, Division Metallic Biomaterials, , Helmholtz-Zentrum Geesthacht, ; Geesthacht, Germany
                [5 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Department of Neurosurgery, , Medical University Graz, ; Graz, Austria
                Article
                5969
                10.1007/s10856-017-5969-5
                5585274
                28875381
                f83671b3-edc8-42bd-9e80-ac21e24d3f2f
                © The Author(s) 2017

                This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 20 June 2017
                : 24 August 2017
                Funding
                Funded by: People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme
                Funded by: Austrian society of bone and mineral research-OEGKM
                Funded by: Laura Bassi Centre of Expertise-BRIC (Bioresorbable Implants for Children)
                Funded by: department of orthopedics and trauma surgery, medical university Graz
                Categories
                Clinical Applications of Biomaterials
                Custom metadata
                © Springer Science+Business Media, LLC 2017

                Materials science
                Materials science

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