This article is part of the Research Topic Novel Extracellular Signalling Mechanisms in Bone

Mini Review ARTICLE

Front. Endocrinol., 06 August 2012 |

Glutamate signaling in bone

  • 1 Department of Physiology and Pharmacology, Bristol University, Bristol, UK
  • 2 School of Biosciences, Cardiff University, Cardiff, UK

Mechanical loading plays a key role in the physiology of bone, allowing bone to functionally adapt to its environment, however characterization of the signaling events linking load to bone formation is incomplete. A screen for genes associated with mechanical load-induced bone formation identified the glutamate transporter GLAST, implicating the excitatory amino acid, glutamate, in the mechanoresponse. When an osteogenic load (10 N, 10 Hz) was externally applied to the rat ulna, GLAST (EAAT1) mRNA, was significantly down-regulated in osteocytes in the loaded limb. Functional components from each stage of the glutamate signaling pathway have since been identified within bone, including proteins necessary for calcium-mediated glutamate exocytosis, receptors, transporters, and signal propagation. Activation of ionotropic glutamate receptors has been shown to regulate the phenotype of osteoblasts and osteoclasts in vitro and bone mass in vivo. Furthermore, glutamatergic nerves have been identified in the vicinity of bone cells expressing glutamate receptors in vivo. However, it is not yet known how a glutamate signaling event is initiated in bone or its physiological significance. This review will examine the role of the glutamate signaling pathway in bone, with emphasis on the functions of glutamate transporters in osteoblasts.

Keywords: glutamate, bone, osteoblast, EAAT

Citation: Brakspear KS and Mason DJ (2012) Glutamate signaling in bone. Front. Endocrin. 3:97. doi: 10.3389/fendo.2012.00097

Received: 01 May 2012; Paper pending published: 21 May 2012;
Accepted: 22 July 2012; Published online: 06 August 2012.

Edited by:

Alison Gartland, The University of Sheffield, UK

Reviewed by:

Niklas Rye Jørgensen, Copenhagen University Hospital Glostrup, Denmark
Chantal Chenu, Royal Veterinary College, UK

Copyright: © 2012 Brakspear and Mason. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Deborah J. Mason, School of Biosciences, Cardiff University, Biomedical Sciences Building, Museum Avenue, Cardiff CF10 3AX, UK. e-mail: