Amino acids as signaling molecules modulating bone turnover

Kehong Ding, Michael Cain, Michael Davis, Clare M Bergson, Meghan Elizabeth McGee Lawrence, Crystal Perkins, Trevor Hardigan, Xing Ming Shi, Qing Zhong, Jianrui Xu, Wendy B Bollag, William D Hill, Mohammed Elsayed Elsalanty, David M Hunter, Maria C. Isales, Patricia Lopez, Mark W Hamrick, Carlos M Isales

Research output: Contribution to journalReview article

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)15-24
Number of pages10
JournalBone
Volume115
DOIs
StatePublished - Oct 2018

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Bone Remodeling
Amino Acids
Protein-Restricted Diet
Mesenchymal Stromal Cells
Calcium-Sensing Receptors
Bone and Bones
Aromatic Amino Acids
Food
Bone Density
Essential Amino Acids
Dietary Proteins
G-Protein-Coupled Receptors
Energy Intake
Cell Survival
Nitrogen
Phosphorylation
Ions
Calcium

Keywords

  • Amino acids
  • Nutrients
  • Signaling
  • Stem cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Amino acids as signaling molecules modulating bone turnover. / Ding, Kehong; Cain, Michael; Davis, Michael; Bergson, Clare M; McGee Lawrence, Meghan Elizabeth; Perkins, Crystal; Hardigan, Trevor; Shi, Xing Ming; Zhong, Qing; Xu, Jianrui; Bollag, Wendy B; Hill, William D; Elsalanty, Mohammed Elsayed; Hunter, David M; Isales, Maria C.; Lopez, Patricia; Hamrick, Mark W; Isales, Carlos M.

In: Bone, Vol. 115, 10.2018, p. 15-24.

Research output: Contribution to journalReview article

Ding, Kehong ; Cain, Michael ; Davis, Michael ; Bergson, Clare M ; McGee Lawrence, Meghan Elizabeth ; Perkins, Crystal ; Hardigan, Trevor ; Shi, Xing Ming ; Zhong, Qing ; Xu, Jianrui ; Bollag, Wendy B ; Hill, William D ; Elsalanty, Mohammed Elsayed ; Hunter, David M ; Isales, Maria C. ; Lopez, Patricia ; Hamrick, Mark W ; Isales, Carlos M. / Amino acids as signaling molecules modulating bone turnover. In: Bone. 2018 ; Vol. 115. pp. 15-24.
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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.",
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AU - Ding, Kehong

AU - Cain, Michael

AU - Davis, Michael

AU - Bergson, Clare M

AU - McGee Lawrence, Meghan Elizabeth

AU - Perkins, Crystal

AU - Hardigan, Trevor

AU - Shi, Xing Ming

AU - Zhong, Qing

AU - Xu, Jianrui

AU - Bollag, Wendy B

AU - Hill, William D

AU - Elsalanty, Mohammed Elsayed

AU - Hunter, David M

AU - Isales, Maria C.

AU - Lopez, Patricia

AU - Hamrick, Mark W

AU - Isales, Carlos M

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N2 - 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.

AB - 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.

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