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: Mona El Refaey, Christopher P Watkins, Eileen J Kennedy, Andrew Chang, Qing Zhong, Ke-Hong Ding, Xing-ming Shi, Jianrui Xu, Wendy B Bollag, William D Hill, Maribeth Johnson, Monte Hunter, Mark W Hamrick, Carlos M Isales
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 410 Pg. 87-96 (Jul 15 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 25637715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Amino Acids, Aromatic
• Anabolic Agents
• Tyrosine
• Tryptophan

Topics

• Amino Acids, Aromatic (chemistry, pharmacology)
• Anabolic Agents (chemistry, pharmacology)
• Animals
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• MAP Kinase Signaling System (drug effects)
• Mesenchymal Stem Cells (drug effects)
• Mice
• Osteoporosis (etiology)
• Oxidation-Reduction
• Tryptophan (chemistry, pharmacology)
• Tyrosine (chemistry, pharmacology)