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Mitochondrial DNA from osteoarthritic patients drives functional impairment of mitochondrial activity: a study on transmitochondrial cybrids
Authors:Andrea Dalmao-Fernández  Tamara Hermida-Gómez  Jenny Lund  Maria E. Vazquez-Mosquera  Ignacio Rego-Pérez  Rafael Garesse  Francisco J. Blanco  Mercedes Fernández-Moreno
Affiliation:1. Grupo de investigación en Reumatología, Servicio de Reumatología. Instituto de Investigación Biomédica de A Coruña, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain;2. Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway;3. Departamento de Bioquímica, Instituto de Investigaciones Biomédicas “Alberto Sols,” Madrid, Spain;4. Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain;1. Department of Hematology and Cell Therapy, Oran, Algeria;2. European Society for Blood and Marrow Transplantation Global Committee, Paris, France;3. Institut Paoli Calmettes, Cancer Research Center of Marseille, Aix Marseille University, Marseille, France;4. Department of Hematology and Cell Therapy, Centre Hospitalier Universitaire, Nantes, France;5. University College London Cancer Institute, London, UK;6. Department of Hematology and Cell Therapy, Hospices Civils, Lyon, France;7. Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland;8. University of Freiburg, Freiburg, Germany;9. Policlinico Universitario Tor Vergata, Rome, Italy;10. Department of Hematology and Stem Cell Transplantation, Centre Hospitalier Universitaire, Bordeaux, France;11. Department of Hematology and Cell Therapy, Hôpital Saint-Antoine, Sorbonne University, Paris, France;1. Center for Autoimmune Genomics and Etiology, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;2. Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;3. Immunology Graduate Training Program, Cincinnati, Ohio, USA;4. Molecular and Developmental Biology Graduate Program, Cincinnati, Ohio, USA;5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA;6. Division of Rheumatology, Cincinnati Children''s Hospital Medical Center, Cincinnati, Ohio, USA;1. Biomedical Ethics Research Program, Mayo Clinic, Rochester, Minnesota, USA;2. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA;3. Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, Indiana, USA;4. Department of Anatomy and Neuroscience, Centre for Stem Cell Systems, University of Melbourne, Parkville, Australia;5. Division of Pulmonary and Critical Care Medicine and Biomedical Ethics Research Program, Mayo Clinic, Rochester, Minnesota, USA;6. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA;7. Department of Orthopedic Surgery and Center for Regenerative Medicine, Mayo Clinic College of Medicine, Jacksonville, Florida, USA;8. Biomedical Ethics Research Program and Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA;1. Elite Regenerative Stem Cell Specialists, LLC, Johnstown, Colorado, USA;2. R&D Regenerative Laboratory Resources, LLC, Johnstown, Colorado, USA;3. Colorado Spine Institute, PLLC, Johnstown, Colorado, USA;1. McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA;2. Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA;3. Wake Forest Baptist Medical Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA;4. College of Arts and Sciences, Ohio State University, Columbus, Ohio, USA;5. Cellf Bio LLC, Winston-Salem, North Carolina, USA;6. Department of Medicine, Gastroenterology Unit, Giambattista Rossi University Hospital, University Hospital Integrated Trust of Verona, University of Verona, Verona, Italy;1. Seattle Children''s Research Institute, Seattle, Washington, USA;2. University of California San Francisco, San Francisco, California, USA;3. Children''s Hospital Los Angeles, Los Angeles, California, USA;4. Center for Cancer and Immunology Research, Center for Cancer and Blood Disorders, Children''s National Hospital, Washington, DC, USA;5. The George Washington University, Washington, DC, USA
Abstract:With the redefinition of osteoarthritis (OA) and the understanding that the joint behaves as an organ, OA is now considered a systemic illness with a low grade of chronic inflammation. Mitochondrial dysfunction is well documented in OA and has the capacity to alter chondrocyte and synoviocyte function. Transmitochondrial cybrids are suggested as a useful cellular model to study mitochondrial biology in vitro, as they carry different mitochondrial variants with the same nuclear background. The aim of this work was to study mitochondrial and metabolic function of cybrids with mitochondrial DNA from healthy (N) and OA donors. In this work, the authors demonstrate that cybrids from OA patients behave differently from cybrids from N donors in several mitochondrial parameters. Furthermore, OA cybrids behave similarly to OA chondrocytes. These results enhance our understanding of the role of mitochondria in the degeneration process of OA and present cybrids as a useful model to study OA pathogenesis.
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