Functional Glutamate Signaling in Bone
Functional Glutamate Signaling in Bone
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DOI：
10.1002/chin.201105262
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发表时间：
2011-02
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影响因子：
--
通讯作者：
E. Hinoi
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文献类型：
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作者：
E. Hinoi
谷氨酸（Glu）被认为是哺乳动物中枢神经系统中的兴奋性氨基酸神经递质。相对较少的关注已支付的功能表达的Glu信号转导机制在外周组织。因此，在这篇综述中，我们总结了可能的信号通过谷氨酸作为细胞外信号介质的机制，维持细胞内稳态的骨组织。在成骨细胞中发现了特定Glu受体（GluR）、Glu转运体（GluT）的mRNA的组成性表达。N-甲基-D-天冬氨酸受体拮抗剂MK-801通过调节Runx 2的表达，显著抑制成骨细胞的分化和成熟。DL-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸通过成骨细胞表达的内源性Glu受体显著增加成骨细胞释放内源性Glu。此外，[3 H] Glu摄取也以温度和钠依赖性方式观察到，其药理学特征与成骨细胞中脑GluTs的药理学特征相似。虽然在原代培养的小鼠破骨细胞中没有发现所有GluRs的mRNA表达，但在GluT中发现了mRNA的组成型表达，如兴奋性氨基酸转运蛋白和胱氨酸/Glu反向转运蛋白。谷氨酸显着抑制破骨细胞生成的方式敏感的反向转运蛋白抑制剂。全身给药的Glu显着防止骨密度降低，除了增加骨质疏松症指数在卵巢切除小鼠体内。两者合计，谷氨酸可以发挥关键作用的机制，维持细胞内稳态的细胞外信号介质在骨。
L-glutamate (Glu) has been thought to be an excitatory amino acid neurotransmitter in the mammalian central nervous system. Relatively little attention has been paid to the functional expression of Glu signaling machineries in peripheral tissues. In this review, therefore, we summarized the possible signaling by Glu as an extracellular signal mediator in mechanisms underlying maintenance of cellular homeostasis in bone tissues. Constitutive expression of mRNAs for particular Glu receptors (GluR), Glu transporters (GluT) was found in osteoblasts. N-methyl-D-aspartic acid receptor antagonist MK-801 significantly prevented differentiation and maturation of osteoblasts through modulation of expression of Runx2. DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid significantly increased the release of endogenous Glu from osteoblasts through its receptor expressed by osteoblasts. In addition,[3H] Glu uptake was also seen in a temperature-and sodium-dependent manner with pharmacological profiles similar to those for brain GluTs in osteoblasts. Although no mRNA expression was found for all GluRs examined in primary cultured mouse osteoclasts, constitutive expression of mRNAs was seen with GluT, such as excitatory amino acid transporters and cystine/Glu antiporter. Glu markedly inhibited osteoclastogenesis in a manner sensitive to the antiporter inhibitor. The systemic administration of Glu significantly prevented the decreased bone mineral density in addition to increased osteoclastic indices in ovariectomized mice in vivo. Taken together, Glu could play a pivotal role in mechanisms underlying the maintenance of cellular homeostasis as an extracellular signal mediator in bone.