Spontaneous oscillation and mechanically induced calcium waves in chondrocytes

Abstract

The characteristics of spontaneous calcium (Ca(2+)) oscillation and mechanically induced Ca(2+) waves in articular chondrocytes were studied. In some, but not all, chondrocytes in sliced cartilage and primary cultures, we observed spontaneous oscillation of intracellular Ca(2+) that never spread to adjacent cells. In contrast, a mechanical stimulus to a single cell by touching with a glass rod induced an increase of intracellular Ca(2+) that spread to neighboring cells in a wave-like manner, even though there was no physical contact between the cells. This indicated the release of some paracrine factor from the mechanically stimulated cells. Application of ultrasonic vibration also induced an oscillation of intracellular Ca(2+). The application of a uridine 5'-triphosphate (UTP), UTP, induced a transient increase in intracellular Ca(2+) and the release of adenosine 5'-triphosphate (ATP) in cultured chondrocytes. A P2 receptor antagonist (suramin) and blockers of Cl(-) channels, niflumic acid and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), reduced the UTP-induced ATP release. The results indicated that Cl(-) channels were involved in the extracellular release of ATP following mechanical or P2Y receptor stimulation. Thus, ATP stimulation of P2Y receptors elicits an increase in intracellular Ca(2+), triggering further release of ATP from adjacent cells, thereby expanding the Ca(2+) wave in chondrocytes.

ATP release from non-excitable cells

“…Non-stimulated cells in culture and intact tissues often display spontaneous [Ca 2+ ] i oscillations [88,[116][117][118][119] [109,117,118]. Taken together, these findings suggest that spontaneous [Ca 2+ ] i oscillations in different cellular systems may reflect the basal property of cells to release and sense ATP.…”

“…However, [Ca 2+ ] i waves often cross small cell-free areas and are blocked by extracellular ATP scavenging or P2 receptor blockade [88][89][90]. Thus, travelling [Ca 2+ ] i waves can also be caused by release of nucleotides, stimulation of P2 receptors and generation of further nucleotide release to feed wave propagation.…”

The role of purinergic signalling in the musculoskeletal system

“…the P2Y2 receptor) show more limited spatial expression . A number of investigations have shown increased [Ca 2+ ]I levels following treatment with ATP, ADP or UDP, indicating the presence of functional P2 receptors on chondrocytes (Bulman et al, 1995;Hung et al, 1997;Kono et al, 2006).…”

Purinergic signalling in the musculoskeletal system

“…ATP also elevated [Ca 2+ ] i in retinoic acid-treated embryonic chondrocytes [305] and induced increases in [Ca 2+ ] i in human chondrons (chondrocytes surrounded by their native pericellular matrix and cultured in three-dimensional agarose films) [306]. In addition, UTP caused a transient increase in [Ca 2+ ] i and the release of ATP from cultured chondrocytes, effects that were reduced by suramin and blockers of Cl − channels [307].…”

“…Similarly, the increased [Ca 2+ ] i which is observed in articular chondrocytes following fluid flow [328] and pressure-induced strain [329] is probably due to the release of ATP. Additionally, ATP stimulation of P2Y receptors elicits an increase in intracellular [Ca 2+ ] i which triggers further release of ATP from adjacent cells, thereby enhancing Ca 2+ waves in chondrocytes [307]. There has been a recent report that 100 μM ATP induced massive release of ATP from articular chondrocytes, probably as the result of P2X7 receptor activation [330].…”