Department of Pathology and Molecular Medicine, McMaster University Hamilton, ON, Canada.
Front Endocrinol (Lausanne). 2012 Jul 19;3:89. doi: 10.3389/fendo.2012.00089. eCollection 2012.
Bone relies on multiple extracellular signaling systems to maintain homeostasis of its normal structure and functions. The amino acid glutamate is a fundamental extracellular messenger molecule in many tissues, and is used in bone for both neural and non-neural signaling. This review focuses on the non-neural interactions, and examines the evolutionarily ancient glutamate signaling system in the context of its application to normal bone functioning and discusses recent findings on the role of glutamate signaling as they pertain to maintaining healthy bone structure. The underlying mechanisms of glutamate signaling and the many roles glutamate plays in modulating bone physiology are featured, including those involved in osteoclast and osteoblast differentiation and mature cell functions. Moreover, the relevance of glutamate signaling systems in diseases that affect bone, such as cancer and rheumatoid arthritis, is discussed, and will highlight how the glutamate system may be exploited as a viable therapeutic target. We will identify novel areas of research where knowledge of glutamate communication mechanisms may aid in our understanding of the complex nature of bone homeostasis. By uncovering the contributions of glutamate in maintaining healthy bone, the reader will discover how this complex molecular signaling system may advance our capacity to treat bone pathologies.
骨骼依靠多种细胞外信号系统来维持其正常结构和功能的稳态。氨基酸谷氨酸是许多组织中基本的细胞外信使分子，在骨骼中用于神经和非神经信号传递。本综述重点关注非神经相互作用，并在正常骨骼功能应用的背景下研究古老的谷氨酸信号系统，并讨论谷氨酸信号在维持健康骨骼结构方面的最新发现。突出了谷氨酸信号的潜在机制及其在调节骨骼生理学中的多种作用，包括参与破骨细胞和成骨细胞分化以及成熟细胞功能的作用。此外，还讨论了影响骨骼的疾病（如癌症和类风湿关节炎）中谷氨酸信号系统的相关性，并强调了谷氨酸系统如何作为可行的治疗靶点加以利用。我们将确定新的研究领域，在这些领域中，对谷氨酸通讯机制的了解可能有助于我们理解骨骼稳态的复杂性质。通过揭示谷氨酸在维持健康骨骼中的作用，读者将发现这种复杂的分子信号系统如何提高我们治疗骨骼病理学的能力。
