PMID- 15299260
OWN - NLM
STAT- MEDLINE
DCOM- 20041214
LR  - 20131121
IS  - 0006-355X (Print)
IS  - 0006-355X (Linking)
VI  - 41
IP  - 3-4
DP  - 2004
TI  - NMDA receptor expression and roles in human articular chondrocyte 
      mechanotransduction.
PG  - 273-81
AB  - Mechanical forces influence articular cartilage structure by regulating 
      chondrocyte activity. Mechanical stimulation results in activation of an 
      alpha5beta1 integrin dependent intracellular signal cascade involving focal 
      adhesion kinase and protein kinase C, triggering the release of interleukin-4 
      from the cell. In normal HAC the response to physiological mechanical stimulation 
      is characterised by increased levels of aggrecan mRNA and a decrease in levels of 
      mRNA for matrix metalloproteinase 3 (MMP-3), the net result of which would be to 
      maintain and optimise cartilage structure and function. This protective/anabolic 
      response is not seen when chondrocytes from osteoarthritic cartilage are 
      subjected to an identical mechanical stimulation regime. Following the 
      observation that the neurotransmitter substance P is involved in chondrocyte 
      mechanotransduction the present study was undertaken to establish potential roles 
      for glutamate receptors in the control of chondrocyte mechanical responses. Using 
      immunohistochemistry and RTPCR normal and OA chondrocytes are shown to express 
      NR1 and NR2a subunits of the NMDA receptor. Addition of NMDA receptor agonists to 
      chondrocytes in primary culture resulted in changes in membrane potential 
      consistent with expression of functional receptors. NMDA receptor antagonists 
      inhibited the hyperpolarisation response of normal chondrocytes to mechanical 
      stimulation but had no effect on the depolarisation response of osteoarthritic 
      chondrocytes to mechanical stimulation. These studies indicate that at least one 
      subset of the NMDA receptor family of molecules is expressed in cartilage and may 
      have important modulatory effects on mechanotransduction and cellular responses 
      following mechanical stimulation. Indeed the results suggest that there is an 
      alteration of NMDA receptor signalling in OA chondrocytes, which may be critical 
      in the abnormal response of OA chondrocytes to mechanical stimulation. Thus NMDA 
      receptors appear to be involved in the regulation of human articular chondrocyte 
      responses to mechanical stimulation, and in OA, mechanotransduction pathways may 
      be modified as a result of altered activation and function of these receptors.
FAU - Salter, D M
AU  - Salter DM
AD  - College of Medicine and Veterinary Medicine, Edinburgh University, Edinburgh, UK. 
      Donald.Salter@ed.ac.uk
FAU - Wright, M O
AU  - Wright MO
FAU - Millward-Sadler, S J
AU  - Millward-Sadler SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biorheology
JT  - Biorheology
JID - 0372526
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Organophosphonates)
RN  - 0 (Piperazines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (carboxypiperazinyl propylphosphonic acid)
RN  - 0 (methyl-(4-carboxyphenyl)glycine)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - *Cartilage, Articular
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glycine/*analogs & derivatives/pharmacology
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - *Mechanotransduction, Cellular
MH  - Membrane Potentials/drug effects
MH  - Organophosphonates/pharmacology
MH  - Osteoarthritis/*metabolism
MH  - Piperazines/pharmacology
MH  - Pressure
MH  - RNA, Messenger/analysis
MH  - Receptors, N-Methyl-D-Aspartate/analysis/antagonists & inhibitors/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2004/08/10 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/08/10 05:00
PHST- 2004/08/10 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/08/10 05:00 [entrez]
PST - ppublish
SO  - Biorheology. 2004;41(3-4):273-81.