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

Mona El Refaey, Christopher P. Watkins, Eileen J. Kennedy, Andrew Chang, Qing Zhong, Kehong Ding, Xing Ming Shi, Jianrui Xu, Wendy B Bollag, William D Hill, Maribeth H Johnson, David M Hunter, Mark W Hamrick, Carlos M Isales

Research output: Contribution to journalReview article

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume410
DOIs
StatePublished - Jul 5 2015

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Anabolic Agents
Aromatic Amino Acids
Stem cells
Mesenchymal Stromal Cells
Tryptophan
Tyrosine
Bone
Bone Marrow
Amino Acids
Oxidation
Osteoporosis
Kynurenine
Bone and Bones
Reactive Oxygen Species
Osteocalcin
Bone Resorption
Mitogen-Activated Protein Kinases
Osteogenesis
Oxides
Alkaline Phosphatase

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells. / El Refaey, Mona; Watkins, Christopher P.; Kennedy, Eileen J.; Chang, Andrew; Zhong, Qing; Ding, Kehong; Shi, Xing Ming; Xu, Jianrui; Bollag, Wendy B; Hill, William D; Johnson, Maribeth H; Hunter, David M; Hamrick, Mark W; Isales, Carlos M.

In: Molecular and Cellular Endocrinology, Vol. 410, 05.07.2015, p. 87-96.

Research output: Contribution to journalReview article

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AU - Watkins, Christopher P.

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AU - Ding, Kehong

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