PMID- 15758455
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20050509
LR  - 20050310
IS  - 1108-7161 (Print)
IS  - 1108-7161 (Linking)
VI  - 2
IP  - 3
DP  - 2002 Mar
TI  - Glutamatergic regulation of bone remodeling.
PG  - 282-4
AB  - L-glutamate (Glu) is the predominant neuromediator in the mammalian central 
      nervous system (CNS). Bone is highly innervated and there is growing evidence of 
      a neural control of bone cell metabolism. The recent discovery of Glu-containing 
      nerve fibers in bone and Glu receptors (GluR) and transporters in bone cells 
      suggest that this neuromediator may also act as a signaling molecule in bone and 
      regulate bone cell function. Our previous studies have demonstrated that 
      ionotropic N-Methyl-D-Aspartate (NMDA) GluR are highly expressed by mammalian 
      osteoclasts. NMDA receptors (NMDAR) are heteromers associating the NR1 subunit 
      and one of the four types of NR2 subunits (NR2A to D). We showed that osteoclasts 
      express NR1, NR2B and NR2D subunits, suggesting a molecular diversity of NMDAR in 
      these cells. Electrophysiological studies have confirmed that NMDAR are 
      functional in mature osteoclasts, and features of Glu-induced current recorded in 
      these cells indicate a major NR2D subunit composition. Using an in vitro assay of 
      bone resorption, we showed that several antagonists of NMDAR binding to different 
      sites of the receptor inhibit bone resorption. In particular, the specific NMDAR 
      channel blocker MK801 had no effect on osteoclast attachment to bone and survival 
      while it rapidly decreased the percentage of osteoclasts with actin ring 
      structures that are associated with actively resorbing osteoclasts. NMDAR may 
      thus be involved in adhesion-induced formation of the sealing zone required for 
      bone resorption. NMDAR are also expressed by osteoclast precursors isolated from 
      mouse bone marrow. We recently confirmed the presence of NR1, NR2B and NR2D in 
      these cells and demonstrated their expression at all differentiation stages from 
      osteoclast precursors to mature resorbing osteoclasts. No regulation of these 
      subunits mRNA expression levels was observed throughout the osteoclastic 
      differentiation sequence. Activation of NMDAR may therefore represent a new 
      mechanism for regulating osteoclast formation and activity. While the origin of 
      Glu in bone is still unknown, the possibility of a glutamatergic 
      neurotransmission in this tissue is suggested by the detection of Glu in nerve 
      fibers in close contact to bone cells. Furthermore, we recently demonstrated that 
      sciatic neurectomy in growing rats induces a bone loss associated with a 
      reduction of nerve profiles immunostained for Glu. These results suggest that Glu 
      may be released from glutamatergic nerve profiles present in bone and therefore 
      contribute to the local regulation of bone cell function.
FAU - Chenu, C
AU  - Chenu C
AD  - INSERM Unit 403, Hopital E. Herriot, Pavillon F, Lyon, France. 
      chenu@lyon151.inserm.fr
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - J Musculoskelet Neuronal Interact
JT  - Journal of musculoskeletal & neuronal interactions
JID - 101084496
EDAT- 2005/03/11 09:00
MHDA- 2005/03/11 09:01
CRDT- 2005/03/11 09:00
PHST- 2005/03/11 09:00 [pubmed]
PHST- 2005/03/11 09:01 [medline]
PHST- 2005/03/11 09:00 [entrez]
PST - ppublish
SO  - J Musculoskelet Neuronal Interact. 2002 Mar;2(3):282-4.