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Effects of extracellular magnesium on the differentiation and function of human osteoclasts
Institution:1. Institute of Materials Research, Department for Structural Research on Macromolecules, Helmholtz-Zentrum Geesthacht (HZG), Geesthacht, Germany;2. Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany;1. Department of Orthopedics, Tenth People’s Hospital, Shanghai Tong Ji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, People’s Republic of China;2. The First Clinical Medical College, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, People’s Republic of China;3. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, People’s Republic of China;1. Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA;2. The Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA;3. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA;4. The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA;5. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA;1. Department of Orthopaedics, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of China;2. National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai 200240, People’s Republic of China;1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People''s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People''s Republic of China;2. Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, People''s Republic of China;3. Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, People''s Republic of China;4. Engineering Research Center of Digital Medicine and Clinical Translation, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200011, People''s Republic of China
Abstract:Magnesium-based implants have been shown to influence the surrounding bone structure. In an attempt to partially reveal the cellular mechanisms involved in the remodelling of magnesium-based implants, the influence of increased extracellular magnesium content on human osteoclasts was studied. Peripheral blood mononuclear cells were driven towards an osteoclastogenesis pathway via stimulation with receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor for 28 days. Concomitantly, the cultures were exposed to variable magnesium concentrations (from either magnesium chloride or magnesium extracts). Osteoclast proliferation and differentiation were evaluated based on cell metabolic activity, total protein content, tartrate-resistant acid phosphatase activity, cathepsin K and calcitonin receptor immunocytochemistry, and cellular ability to form resorption pits. While magnesium chloride first enhanced and then opposed cell proliferation and differentiation in a concentration-dependent manner (peaking between 10 and 15 mM magnesium chloride), magnesium extracts (with lower magnesium contents) appeared to decrease cell metabolic activity (≈50% decrease at day 28) while increasing osteoclast activity at a lower concentration (twofold higher). Together, the results indicated that (i) variations in the in vitro extracellular magnesium concentration affect osteoclast metabolism and (ii) magnesium extracts should be used preferentially in vitro to more closely mimic the in vivo environment.
Keywords:Osteoclast  Magnesium  Biodegradation  Primary cells  Cell culture
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