Edinburgh Napier University

  Purpose: Classical neuronal signalling molecules such as substance P and glutamate have been identified in cartilage and are being shown to have roles in regulation of chondrocyte function. This study looks at the expression and function of the metabotropic glutamate NMDA receptor (NMDAR) in OA chondrocytes.
Methods: Chondrocytes from articular cartilage of human knee joint arthroplasty specimens. NMDAR subunit expression at gene an protein levels was identified by RTPCR and western blotting. NMDAR function was assayed using radolabelled Ca45 uptake and changes in cell membrane potential in response to NMDA and mechanical stimulation (MS; electrophys. only) in the presence and absence of the NMDA antagonists MK801 (noncompetitive), Ifenprodil (NR2B selective) and APV (competitive).
Results: NMDAR1, 2A, and 2B, but not NR2C, 2D and 3, were detected at varying levels in OA chondrocytes at both the protein and RNA levels. Assessment of receptor function showed that OA chondrocytes responded to NMDA; this response was decreased by specific antagonists. NMDA induced an increase in Ca45 uptake which was reduced to baseline by the antagonists. Both NMDA and mechanical stimulation induced a membrane depolarisation which was decreased or abolished by NMDAR antagonists.
Conclusions: This study shows the presence of functional NMDA receptors composed of NR1, 2A and 2B subunits on human OA chondrocytes. It has been suggested that the NMDA receptor is a mechanosensitive receptor in neurones and the current investigation suggests similar involvement in chondrocyte mechanotransduction.