Reprint of "The detection of knee joint sounds at defined loads by means of vibroarthrography".

BACKGROUND: Crepitus of the knee may mirror structural and functional changes in the joint during motion. Although the magnitude of these sounds increases with greater cartilage damage, it is unclear whether knee joint sounds also reflect joint loading. METHODS: Twelve healthy volunteers (mean 26 (SD 3.6) years, 7 females) participated in the randomized-balanced crossover study. Knee joint sounds were recorded (linear sampling, 5512 Hz) by means of two microphones, one placed on the medial tibial plateau and one on the patella. Two activities of daily living (standing up from/sitting down on a bench; descending stairs) and three open kinetic chain knee extension-flexion cycles (passive movement, 10% and 40% loading of the individual one repetition maximum) were performed. Each participant carried out three sets of five repetitions and three sets of 15 steps downwards (stairs), respectively. For data analysis, the mean sound amplitude and the median power frequency for each loading condition were determined. Friedman test and Bonferroni-Holm adjusted post-hoc test were performed to detect differences between conditions. FINDINGS: We obtained significant differences between joint sound amplitudes for all movements, both measured at the medial tibial plateau (Chi2 = 20.7, p < 0.001) and at the patella (Chi2 = 27.6, p < 0.001). We showed a significant difference in the median power frequency of the patella between all movements (Chi2 = 17.8, p < 0.5). INTERPRETATION: Overall, the larger the supposed knee joint loading was, the louder was the recorded knee crepitus. Consequently, vibroarthrographically assessed knee joint sounds can differ across knee joint loading conditions.

Reliability of Vibroarthrography to Assess Knee Joint Sounds in Motion.

Knee acoustic emissions provide information about joint health and loading in motion. As the reproducibility of knee acoustic emissions by vibroarthrography is yet unknown, we evaluated the intrasession and interday reliability of knee joint sounds. In 19 volunteers (25.6 ± 2.0 years, 11 female), knee joint sounds were recorded by two acoustic sensors (16,000 Hz; medial tibial plateau, patella). All participants performed four sets standing up/sitting down (five repetitions each). For measuring intrasession reliability, we used a washout phase of 30 min between the first three sets, and for interday reliability we used a washout phase of one week between sets 3 and 4. The mean amplitude (dB) and median power frequency (Hz, MPF) were analyzed for each set. Intraclass correlation coefficients (ICCs (2,1)), standard errors of measurement (SEMs), and coefficients of variability (CVs) were calculated. The intrasession ICCs ranged from 0.85 to 0.95 (tibia) and from 0.73 to 0.87 (patella). The corresponding SEMs for the amplitude were ≤1.44 dB (tibia) and ≤2.38 dB (patella); for the MPF, SEMs were ≤13.78 Hz (tibia) and ≤14.47 Hz (patella). The intrasession CVs were ≤0.06 (tibia) and ≤0.07 (patella) (p < 0.05). The interday ICCs ranged from 0.24 to 0.33 (tibia) and from 0 to 0.82 (patella) for both the MPF and amplitude. The interday SEMs were ≤4.39 dB (tibia) and ≤6.85 dB (patella) for the amplitude and ≤35.39 Hz (tibia) and ≤15.64 Hz (patella) for the MPF. The CVs were ≤0.14 (tibia) and ≤0.08 (patella). Knee joint sounds were highly repeatable within a single session but yielded inconsistent results for the interday reliability.

The detection of knee joint sounds at defined loads by means of vibroarthrography.

BACKGROUND: Crepitus of the knee may mirror structural and functional changes in the joint during motion. Although the magnitude of these sounds increases with greater cartilage damage, it is unclear whether knee joint sounds also reflect joint loading. METHODS: Twelve healthy volunteers (mean 26 (SD 3.6) years, 7 females) participated in the randomized-balanced crossover study. Knee joint sounds were recorded (linear sampling, 5512 Hz) by means of two microphones, one placed on the medial tibial plateau and one on the patella. Two activities of daily living (standing up from/sitting down on a bench; descending stairs) and three open kinetic chain knee extension-flexion cycles (passive movement, 10% and 40% loading of the individual one repetition maximum) were performed. Each participant carried out three sets of five repetitions and three sets of 15 steps downwards (stairs), respectively. For data analysis, the mean sound amplitude and the median power frequency for each loading condition were determined. Friedman test and Bonferroni-Holm adjusted post-hoc test were performed to detect differences between conditions. FINDINGS: We obtained significant differences between joint sound amplitudes for all movements, both measured at the medial tibial plateau (Chi2 = 20.7, p < 0.001) and at the patella (Chi2 = 27.6, p < 0.001). We showed a significant difference in the median power frequency of the patella between all movements (Chi2 = 17.8, p < 0.5). INTERPRETATION: Overall, the larger the supposed knee joint loading was, the louder was the recorded knee crepitus. Consequently, vibroarthrographically assessed knee joint sounds can differ across knee joint loading conditions.

"Host tissue damage" signal ATP promotes non-directional migration and negatively regulates toll-like receptor signaling in human monocytes.

The activation of Toll-like receptors (TLRs) by lipopolysaccharide or other ligands evokes a proinflammatory immune response, which is not only capable of clearing invading pathogens but can also inflict damage to host tissues. It is therefore important to prevent an overshoot of the TLR-induced response where necessary, and here we show that extracellular ATP is capable of doing this in human monocytes. Using reverse transcription-PCR, we showed that monocytes express P2Y(1), P2Y(2), P2Y(4), P2Y(11), and P2Y(13) receptors, as well as several P2X receptors. To elucidate the function of these receptors, we first studied Ca(2+) signaling in single cells. ATP or UTP induced a biphasic increase in cytosolic Ca(2+), which corresponded to internal Ca(2+) release followed by activation of store-operated Ca(2+) entry. The evoked Ca(2+) signals stimulated Ca(2+)-activated K(+) channels, producing transient membrane hyperpolarization. In addition, ATP promoted cytoskeleton reorganization and cell migration; however, unlike chemoattractants, the migration was non-directional and further analysis showed that ATP did not activate Akt, essential for sensing gradients. When TLR2, TLR4, or TLR2/6 were stimulated with their respective ligands, ATPgammaS profoundly inhibited secretion of proinflammatory cytokines (tumor necrosis factor-alpha and monocyte chemoattractant protein-1) but increased the production of interleukin-10, an anti-inflammatory cytokine. In radioimmune assays, we found that ATP (or ATPgammaS) strongly increased cAMP levels, and, moreover, the TLR-response was inhibited by forskolin, whereas UTP neither increased cAMP nor inhibited the TLR-response. Thus, our data suggest that ATP promotes non-directional migration and, importantly, acts as a "host tissue damage" signal via the G(s) protein-coupled P2Y(11) receptor and increased cAMP to negatively regulate TLR signaling.

Extracellular ATP induces oscillations of intracellular Ca2+ and membrane potential and promotes transcription of IL-6 in macrophages.

The effects of low concentrations of extracellular ATP on cytosolic Ca(2+), membrane potential, and transcription of IL-6 were studied in monocyte-derived human macrophages. During inflammation or infection many cells secrete ATP. We show here that application of 10 microM ATP or 10 microM UTP induces oscillations in cytosolic Ca(2+) with a frequency of approximately 12 min(-1) and oscillations in membrane potential. RT-PCR analysis showed expression of P2Y(1), P2Y(2), P2Y(11), P2X(1), P2X(4), and P2X(7) receptors, large-conductance (KCNMA1 and KCNMB1-4), and intermediate-conductance (KCNN4) Ca(2+)-activated K(+) channels. The Ca(2+)oscillations were unchanged after removal of extracellular Ca(2+), indicating that they were mainly due to movements of Ca(2+) between intracellular compartments. Comparison of the effects of different nucleotides suggests that the Ca(2+) oscillations were elicited by activation of P2Y(2) receptors coupled to phospholipase C. Patch-clamp experiments showed that ATP induced a transient depolarization, probably mediated by activation of P2X(4) receptors, followed by membrane potential oscillations due to opening of Ca(2+)-activated K(+) channels. We also found that 10 microM ATP gamma S increased transcription of IL-6 approximately 40-fold within 2 h. This effect was abolished by blockade of P2Y receptors with 100 microM suramin. Our results suggest that ATP released from inflamed, damaged, or metabolically impaired cells represents a "danger signal" that plays a major role in activating the innate immune system.