title: Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.
abstract: Adipose-derived mesenchymal stem cells (ASC) hold great promise in the treatment of many disorders including musculoskeletal system, cardiovascular and/or endocrine diseases. However, the cytophysiological condition of cells, used for engraftment seems to be fundamental factor that might determine the effectiveness of clinical therapy. In this study we investigated growth kinetics, senescence, accumulation of oxidative stress factors, mitochondrial biogenesis, autophagy and osteogenic differentiation potential of ASC isolated from horses suffered from equine metabolic syndrome (EMS). We demonstrated that EMS condition impairs multipotency/pluripotency in ASCs causes accumulation of reactive oxygen species and mitochondria deterioration. We found that, cytochrome c is released from mitochondria to the cytoplasm suggesting activation of intrinsic apoptotic pathway in those cells. Moreover, we observed up-regulation of p21 and decreased ratio of Bcl-2/BAX. Deteriorations in mitochondria structure caused alternations in osteogenic differentiation of ASCEMSresulting in their decreased proliferation rate and reduced expression of osteogenic markers BMP-2 and collagen type I. During osteogenic differentiation of ASCEMS, we observed autophagic turnover as probably, an alternative way to generate adenosine triphosphate and amino acids required to increased protein synthesis during differentiation. Downregulation of PGC1α, PARKIN and PDK4 in differentiated ASCEMSconfirmed impairments in mitochondrial biogenesis and function. Hence, application of ASCEMSinto endocrinological or ortophedical practice requires further investigation and analysis in the context of safeness of their application.
authors.affiliation: Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw, Wroclaw, Poland.|Wroclaw Research Centre EIT+, Wrocław, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marycz
authors.affiliation: Electron Microscopy Laboratory, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences Wroclaw, Wroclaw, Poland.|Wroclaw Research Centre EIT+, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kornicka
authors.affiliation: Department of Animal Physiology and Biostructure, Faculty of Veterinary Medicine, University of Environmental and Life Sciences Wroclaw, Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Marędziak
authors.affiliation: Equine Clinic Equivet, Gliwice, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Golonka
authors.affiliation: Department of Surgery, Faculty of Veterinary Medicine, University of Environmental and Life Sciences Wroclaw, Wroclaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Nicpoń
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001343:Autophagy; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006736:Horses; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016130:Immunophenotyping; D007700:Kinetics; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D008745:Methylation; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics; D063306:Mitophagy; D039902:Multipotent Stem Cells / Q000166:cytology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D014157:Transcription Factors
keywords: adipose derived stem cells; autophagy; equine metabolic syndrome; mitochondria; mitochondria biogenesis; mitophagy