Modulation of interleukin-6 and matrix metalloproteinase 2 expression in human fibroblast-like synoviocytes by functional ionotropic glutamate receptors

Objective. Patients with rheumatoid arthritis (RA) have increased concentrations of the amino acid glutamate in synovial fluid. This study was undertaken to determine whether glutamate receptors are expressed in the synovial joint, and to determine whether activation of glutamate receptors on human synoviocytes contributes to RA disease pathology. Methods. Glutamate receptor expression was examined in tissue samples from rat knee joints and in human fibroblast-like synoviocytes (FLS). FLS from 5 RA patients and 1 normal control were used to determine whether a range of glutamate receptor antagonists influenced expression of the proinflammatory cytokine interleukin-6 (IL-6), enzymes involved in matrix degradation and cytokine processing (matrix metalloproteinase 2 [MMP-2] and MMP-9), and the inhibitors of these enzymes (tissue inhibitor of metalloproteinases 1 [TIMP-1] and TIMP-2). IL-6 concentrations were determined by enzyme-linked immunosorbent assay, MMP activity was measured by gelatin zymography, and TIMP activity was determined by reverse zymography. Fluorescence imaging of intracellular calcium concentrations in live RA FLS stimulated with specific antagonists was used to reveal functional activation of glutamate receptors that modulated IL-6 or MMP-2. Results. Ionotropic and metabotropic glutamate receptor subunit mRNA were expressed in the patella, fat pad, and meniscus of the rat knee and in human articular cartilage. Inhibition of N-methyl-D-aspartate (NMDA) receptors in RA FLS increased proMMP-2 release, whereas non-NMDA ionotropic glutamate receptor antagonists reduced IL-6 production by these cells. Stimulation with glutamate, NMDA, or kainate (KA) increased intracellular calcium concentrations in RA FLS, demonstrating functional activation of specific ionotropic glutamate receptors. Conclusion. Our findings indicate that activation of NMDA and KA glutamate receptors on human synoviocytes may contribute to joint destruction by increasing IL-6 expression. © 2007, American College of Rheumatology.

Relevance of motion artifact in electromyography recordings during vibration treatment

Electromyography readings (EMGs) from quadriceps of fifteen subjects were recorded during whole body vibration treatment at different frequencies (10-50 Hz). Additional electrodes were placed on the patella to monitor the occurrence of motion artifact, triaxial accelerometers were placed onto quadriceps to monitor motion. Signal spectra revealed sharp peaks corresponding to vibration frequency and its harmonics, in accordance with the accelerometer data. EMG total power was compared to that associated with vibration harmonics narrow bands, before and during vibration. On average, vibration associated power resulted in only 3% (±0.9%) of the total power prior to vibration and 29% (±13.4%) during vibration. Often, studies employ surface EMG to quantitatively evaluate vibration evoked muscular activity and to set stimulation frequency. However, previous research has not accounted for motion artifacts. The data presented in this study emphasize the need for the removal of motion artifacts, as they consistently affect RMS estimation, which is often used as a concise muscle activity index during vibrations. Such artifacts, rather unpredictable in amplitude, might be the cause of large inter-study differences and must be eliminated before analysis. Motion artifact filtering will contribute to thorough and precise interpretation of neuromuscular response to vibration treatment. © 2008 Elsevier Ltd. All rights reserved.