Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells. (15th July 2015)

• Record Type: Journal Article
• Authors: El Refaey, Mona; Watkins, Christopher P.; Kennedy, Eileen J.; Chang, Andrew; Zhong, Qing; Ding, Ke-Hong; Shi, Xing-ming; Xu, Jianrui; Bollag, Wendy B.; Hill, William D.; Johnson, Maribeth; Hunter, Monte; Hamrick, Mark W.; Isales, Carlos M.
• Is Part Of: Molecular and cellular endocrinology. Volume 410(2015)
• Page Start: 87
• Page End: 96
• Publication Date: 2015-07-15
• Subjects: Kynurenine -- Proliferation -- Differentiation -- Amino acids -- Oxidized nutrients -- BMMSCs; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.01.034
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: The aromatic amino acids activate proliferative and differentiation pathways in bone marrow mesenchymal stem cells. Oxidized amino acids are either less potent activators of these signaling pathways or can block their normal activation. ROS can impair BMMSC function both by depleting anabolic amino acids and also by generating inhibitory oxidation products. 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.