Ca 2+ oscillations and intercellular Ca 2+ waves in ATP‐stimulated articular chondrocytes

Cytosolic Ca 2+ oscillations are known to occur in many cell types stimulated with agonists linked to the phosphoinositide signaling pathway. Trains of repetitive short‐lasting Ca 2+ spikes could be induced in articular chondrocytes by extracellular ATP, an agonist potently effective in stimulating cartilage resorption. The mechanism of these Ca 2+ oscillations was studied by computerized video imaging on primary cultures of articular chondrocytes. Few cycles of oscillatory activity could be evoked in the absence of extracellular Ca 2+ , while, for oscillations to be sustained, Ca 2+ influx was required. Thapsigargin irreversibly blocked Ca 2+ oscillations, thus demonstrating the crucial involvement of intracellular stores in triggering the rhythmic activity. Apart from activating intracellular Ca 2+ release, extracellular ATP also induced a noncapacitive Ca 2+ influx in these cells. This ATP‐mediated influx modulates both the oscillation frequency and intracellular stores refilling. In monolayers of confluent cells, Ca 2+ oscillations spread from cell to cell in the form of intercellular waves. Propagating waves could also be observed in the absence of extracellular Ca 2+ , demonstrating that Ca 2+ itself is not required for signal coordination. These results demonstrate that complex spatiotemporal pathways of Ca 2+ oscillations and intercellular Ca 2+ waves could be activated in articular chondrocytes during degenerative diseases. (J Bone Miner Res 1996;11:946‐954)