Amino acids as signaling molecules modulating bone turnover.
Amino acids as signaling molecules modulating bone turnover.
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DOI：
10.1016/j.bone.2018.02.028
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发表时间：
2018-10
期刊：
影响因子：
4.1
通讯作者：
Isales CM
中科院分区：
文献类型：
--
作者：
Ding KH;Cain M;Davis M;Bergson C;McGee-Lawrence M;Perkins C;Hardigan T;Shi X;Zhong Q;Xu J;Bollag WB;Hill W;Elsalanty M;Hunter M;Isales MC;Lopez P;Hamrick M;Isales CM
除了必需氨基酸（AA）之外，对充足膳食蛋白质摄入量的大部分关注都集中在总氮和热量摄入量上，而不是AA组成。然而，最近的数据表明，“氨基酸传感”可以通过细胞内或细胞外营养传感机制发生。特别是，已知3类G蛋白偶联受体家族的成员，如钙敏感受体，优先结合特异性AA，然后通过钙离子调节受体活化，从而潜在地影响骨转换。在追求直接营养对骨细胞的影响的可能性，我们研究了个体AA对骨祖细胞/骨髓基质细胞（BMSC）的影响，这是骨修复的关键目标。我们证明，骨髓基质细胞表达细胞内和细胞外的营养感应途径和AAs所需的骨髓基质细胞的生存。此外，某些AA类型，如芳香族AA的成员，可以有效地刺激细胞内钙和ERK磷酸化/活化的增加。此外，基于体外数据，我们研究了特定AA对骨量的影响。为了更好地评估特定AA的影响，我们将这些添加到低蛋白饮食中。我们的数据表明，低蛋白饮食本身与老年小鼠骨矿物质密度（BMD）的显著下降有关，至少部分与骨代谢活性的增加有关。这种低蛋白饮食小鼠BMD的下降可通过添加芳香族的AA来防止。综上所述，我们的数据表明，氨基酸功能作为特定的和选择性的信号分子在骨细胞。
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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影响因子：
3.7
作者：
Simon BR;Learman BS;Parlee SD;Scheller EL;Mori H;Cawthorn WP;Ning X;Krishnan V;Ma YL;Tyrberg B;MacDougald OA
通讯作者：
MacDougald OA
影响因子：
4.1
作者：
Xie, D;Cheng, H;Isales, CM
通讯作者：
Isales, CM
影响因子：
4.1
作者：
Lee, Heather J.;Mun, Hee-Chang;Conigrave, Arthur D.
通讯作者：
Conigrave, Arthur D.
影响因子：
3.7
作者：
El Refaey M;Zhong Q;Hill WD;Shi XM;Hamrick MW;Bailey L;Johnson M;Xu J;Bollag WB;Chutkan N;Isales CM
通讯作者：
Isales CM
GPRC6A：所有新陈代谢的杰克（或无主人）。
影响因子：
8.1
作者：
Pi M;Nishimoto SK;Quarles LD
通讯作者：
Quarles LD