title: Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells.
abstract: Age-induced bone loss is associated with greater bone resorption and decreased bone formation resulting in osteoporosis and osteoporosis-related fractures. The etiology of this age-induced bone loss is not clear but has been associated with increased generation of reactive oxygen species (ROS) from leaky mitochondria. ROS are known to oxidize/damage the surrounding proteins/amino acids/enzymes and thus impair their normal function. Among the amino acids, the aromatic amino acids are particularly prone to modification by oxidation. Since impaired osteoblastic differentiation from bone marrow mesenchymal stem cells (BMMSCs) plays a role in age-related bone loss, we wished to examine whether oxidized amino acids (in particular the aromatic amino acids) modulated BMMSC function. Using mouse BMMSCs, we examined the effects of the oxidized amino acids di-tyrosine and kynurenine on proliferation, differentiation and Mitogen-Activated Protein Kinase (MAPK) pathway. Our data demonstrate that amino acid oxides (in particular kynurenine) inhibited BMMSC proliferation, alkaline phosphatase expression and activity and the expression of osteogenic markers (Osteocalcin and Runx2). Taken together, our data are consistent with a potential pathogenic role for oxidized amino acids in age-induced bone loss.
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Mona
authors: M
authors: El Refaey
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy University of Georgia, Athens, GA 30602, United States.
authors: Christopher P
authors: CP
authors: Watkins
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy University of Georgia, Athens, GA 30602, United States.
authors: Eileen J
authors: EJ
authors: Kennedy
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Andrew
authors: A
authors: Chang
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Qing
authors: Q
authors: Zhong
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Ke-Hong
authors: KH
authors: Ding
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States.
authors: Xing-ming
authors: XM
authors: Shi
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Jianrui
authors: J
authors: Xu
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Physiology, Georgia Regents University, Augusta, GA, United States; Charlie Norwood VA Medical Center, Augusta, GA 30912, United States.
authors: Wendy B
authors: WB
authors: Bollag
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States; Charlie Norwood VA Medical Center, Augusta, GA 30912, United States; Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, United States.
authors: William D
authors: WD
authors: Hill
authors: Department of Biostatistics, Georgia Regents University, Augusta, GA, United States.
authors: Maribeth
authors: M
authors: Johnson
authors: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States.
authors: Monte
authors: M
authors: Hunter
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States; Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, United States.
authors: Mark W
authors: MW
authors: Hamrick
authors: Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Neuroscience and Regenerative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States; Department of Medicine, Georgia Regents University, Augusta, GA, United States; Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA, United States. Electronic address: cisales@gru.edu.
authors: Carlos M
authors: CM
authors: Isales
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry / Q000494:pharmacology*; D045930:Anabolic Agents / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D010024:Osteoporosis / Q000209:etiology*; D010084:Oxidation-Reduction; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology; D014443:Tyrosine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D024322:Amino Acids, Aromatic; D045930:Anabolic Agents; D014443:Tyrosine; D014364:Tryptophan
keywords: Amino acids; BMMSCs; Differentiation; Kynurenine; Oxidized nutrients; Proliferation
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