title: Metformin Decreases Reactive Oxygen Species, Enhances Osteogenic Properties of Adipose-Derived Multipotent Mesenchymal Stem Cells In Vitro, and Increases Bone Density In Vivo.
abstract: Due to its pleiotropic effects, the commonly used drug metformin has gained renewed interest among medical researchers. While metformin is mainly used for the treatment of diabetes, recent studies suggest that it may have further application in anticancer and antiaging therapies. In this study, we investigated the proliferative potential, accumulation of oxidative stress factors, and osteogenic and adipogenic differentiation potential of mouse adipose-derived stem cells (MuASCs) isolated from mice treated with metformin for 8 weeks. Moreover, we investigated the influence of metformin supplementation on mice bone density and bone element composition. The ASCs isolated from mice who were treated with metformin for 8 weeks showed highest proliferative potential, generated a robust net of cytoskeletal projections, had reduced expression of markers associated with cellular senescence, and decreased amount of reactive oxygen species in comparison to control group. Furthermore, we demonstrated that these cells possessed greatest osteogenic differentiation potential, while their adipogenic differentiation ability was reduced. We also demonstrated that metformin supplementation increases bone density in vivo. Our result stands as a valuable source of data regarding the in vivo influence of metformin on ASCs and bone density and supports a role for metformin in regenerative medicine.
authors.affiliation: Electron Microscopy Laboratory, Wroclaw University of Environmental and Life Sciences, 5b Kozuchowska Street, 51-631 Wroclaw, Poland; Wroclaw Research Centre EIT+, 147 Stablowicka Street, 54-066 Wroclaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marycz
authors.affiliation: Department of Anatomy, Jagiellonian University Medical College, 12 Kopernika Street, 31-034 Krakow, Poland.
authors.forename: Krzysztof A
authors.initials: KA
authors.lastname: Tomaszewski
authors.affiliation: Electron Microscopy Laboratory, Wroclaw University of Environmental and Life Sciences, 5b Kozuchowska Street, 51-631 Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kornicka
authors.affiliation: Department of Anatomy, Jagiellonian University Medical College, 12 Kopernika Street, 31-034 Krakow, Poland.
authors.forename: Brandon Michael
authors.initials: BM
authors.lastname: Henry
authors.affiliation: Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, 30 Mickiewicza Street, 30059 Krakow, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wroński
authors.affiliation: Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, 30 Mickiewicza Street, 30059 Krakow, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Tarasiuk
authors.affiliation: Wroclaw Research Centre EIT+, 147 Stablowicka Street, 54-066 Wroclaw, Poland; Department of Animal Physiology and Biostructure, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 31 Norwida Street, 50-375 Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Maredziak
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D017382:Reactive Oxygen Species; D015675:Osteocalcin; D053495:Osteopontin; D008687:Metformin; D013482:Superoxide Dismutase