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Mol Cell Endocrinol. 2015 Jul 15;410:87-96. doi: 10.1016/j.mce.2015.01.034. Epub 2015 Jan 28.

Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells.

Author information

1
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.
2
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy University of Georgia, Athens, GA 30602, United States.
3
Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States.
4
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.
5
Institute for Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Medicine, Georgia Regents University, Augusta, GA, United States.
6
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.
7
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.
8
Department of Biostatistics, Georgia Regents University, Augusta, GA, United States.
9
Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States.
10
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.
11
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.

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.

KEYWORDS:

Amino acids; BMMSCs; Differentiation; Kynurenine; Oxidized nutrients; Proliferation

PMID:
25637715
PMCID:
PMC4444384
DOI:
10.1016/j.mce.2015.01.034
[Indexed for MEDLINE]
Free PMC Article

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