Amino acids as signaling molecules modulating bone turnover

Abstract

Except for the essential amino acids (AAs), much of the focus on adequate dietary protein intake has been on total nitrogen and caloric intake rather than AA composition. Recent data, however, demonstrate that "amino-acid sensing" can occur through either intracellular or extracellular nutrient-sensing mechanisms. In particular, members of the class 3 G-protein coupled receptor family, like the calcium-sensing receptor are known to preferentially bind specific AAs, which then modulate receptor activation by calcium ions and thus potentially impact bone turnover. In pursuing the possibility of direct nutrient effects on bone cells, we examined individual AA effects on osteoprogenitor/bone marrow stromal cells (BMSCs), a key target for bone anabolism. We demonstrate that BMSCs express both intracellular and extracellular nutrient sensing pathways and that AAs are required for BMSC survival. In addition, certain AA types, like members of the aromatic AAs, can potently stimulate increases in intracellular calcium and ERK phosphorylation/activation. Further, based on the in vitro data, we examined the effect of specific AAs on bone mass. To better evaluate the impact of specific AAs, we added these to a low-protein diet. Our data demonstrate that a low-protein diet itself is associated with a significant drop in bone mineral density (BMD) in the older mice, related, at least in part, to an increase in osteoclastic activity. This drop in BMD in mice on the low-protein diet is prevented by addition of AAs from the aromatic group. Taken together our data show that AAs function as specific and selective signaling molecules in bone cells.

Metabolic Alterations in Older Women With Low Bone Mineral Density Supplemented With Lactobacillus reuteri

“…It has previously been reported that amino acids as signaling molecules modulate bone turnover and are associated with higher BMD. (36,37) Therefore, our data supports that supplementation of the probiotic L.reuteri in this study, will increase the serum amino acid levels that may regulate bone metabolism in older women. Especially, branched chain amino acids (valine) and their derivatives, isovalerylcarnitine (C5), 2-methylbutyrylcarnitine (C5) and isovalerylglycine, increased with the supplementation of L. reuteri.…”

A Multi-Omic Analysis for Low Bone Mineral Density in Postmenopausal Women Suggests a Relationship between Diet, Metabolites, and Microbiota

“…Otherwise, the association between BCAAs and muscle and fat mass may be related to the potential effects on bone health [ 7 ], although both are critical for the maintenance of bone strength and density [ 36 ]. In the case of AAs, the evidence suggests a favorable role in bone health, mainly by promoting osteoblast proliferation and differentiation and acting as signaling molecules in bone cells [ 37 ]. However, their associations with BMD and microbiota composition have not been established in postmenopausal women.…”

The Role of Tryptophan Metabolites in Musculoskeletal Stem Cell Aging

“…Aromatic amino acids (tryptophan, phenylalanine, and tyrosine) are generally known to have antioxidant properties and to play a role in MSC survival and proliferation. Tryptophan (Trp) in particular has been shown to upregulate ERK phosphorylation/activation in bone marrow stromal cells (BMSCs); ERK activation is involved in the cell response to extracellular proliferation signals [12]. Additionally, Trp was found to upregulate the Akt pathway and FOXM1 of an aging BM under normoxic conditions (21% O 2 ).…”