Role of Essential Amino Acids in Age-Induced Bone Loss

Abstract

Age-induced osteoporosis is a global problem. Essential amino acids (EAAs) work as an energy source and a molecular pathway modulator in bone, but their functions have not been systematically reviewed in aging bone. This study aimed to discuss the contribution of EAAs on aging bone from in vitro, in vivo, and human investigations. In aged people with osteoporosis, serum EAAs were detected changing up and down, without a well-established conclusion. The supply of EAAs in aged people either rescued or did not affect bone mineral density (BMD) and bone volume. In most signaling studies, EAAs were proven to increase bone mass. Lysine, threonine, methionine, tryptophan, and isoleucine can increase osteoblast proliferation, activation, and differentiation, and decrease osteoclast activity. Oxidized L-tryptophan promotes bone marrow stem cells (BMSCs) differentiating into osteoblasts. However, the oxidation product of tryptophan called kynurenine increases osteoclast activity, and enhances the differentiation of adipocytes from BMSCs. Taken together, in terms of bone minerals and volume, more views consider EAAs to have a positive effect on aging bone, but the function of EAAs in bone metabolism has not been fully demonstrated and more studies are needed in this area in the future.

Dietary Intake and Circulating Amino Acid Concentrations in Relation with Bone Metabolism Markers in Children Following Vegetarian and Omnivorous Diets

“…Specific AAs may preferentially bind to a calcium-sensing receptor, modulate its activation by calcium ions, and thus potentially impact bone turnover. Amino acids are also required for bone marrow stromal cells to promote differentiation into osteoblasts, synthesis of type I collagen, circulating levels of IGF-I and alkaline phosphatase [ 9 , 10 ]. Certain AA types, particularly amino acids from the aromatic group, can stimulate increases in intracellular calcium and ERK phosphorylation/activation and may impact an early stage of osteoclast differentiation by suppressing the attachment of osteoclasts and the resorption process.…”

“…Recent data demonstrated that AAs should also be viewed as specific and selective signaling molecules in bone cells [ 7 , 8 ]. Bone mass can be elevated by amino acid-induced increases in calcium absorption efficiency, osteoblast proliferation and bone mineralization, synthesis of type I collagen, circulating levels of insulin-like growth factor-I (IGF-I) and alkaline phosphatase, suppressed osteoclast differentiation and reduced bone resorption [ 9 , 10 ]. Certain AA types, particularly amino acids from the aromatic group (phenylalanine, tryptophan, tyrosine) can stimulate an increase in intracellular calcium and extracellular signal-regulated kinase (ERK) phosphorylation/activation [ 8 , 11 ].…”

Glycometabolic reprogramming in cementoblasts: A vital target for enhancing cell mineralization

“…54 For example, threonine can increase osteoblast proliferation and differentiation with decreasing osteoclast activity. 55 Moreover, the presence of nucleotides in the extracellular microenvironment is largely determined by their release from cells and regulates the function of osteoblasts. 56,57 Nucleotides like inosine promote osteoblast proliferation.…”

“…In order to differentiate into fully functional osteoblasts, naive cells in the bone require high amounts of amino acids 54 . For example, threonine can increase osteoblast proliferation and differentiation with decreasing osteoclast activity 55 . Moreover, the presence of nucleotides in the extracellular microenvironment is largely determined by their release from cells and regulates the function of osteoblasts 56,57 .…”

Metabolic Response Modulations by Zwitterionic Hydrogels for Achieving Promoted Bone Regeneration

“…I,J) Enriched KEGG pathways of metabolome response to PAC/GelMA, PDAC/GelMA, and PDMAPS/GelMA on I) day 3 and J) 7. formation. [65] Arachidonic acid, prostaglandin h2, and dinoprostone are classic markers for inflammation, which downregulated bone mineral content. [66] Bile acids, short-chain fatty acids, and trimethylamine N-oxide are the common substances in high-fat diet (HFD)-induced chronic diseases.…”