Mechanism of mechanically induced intercellular calcium waves in rabbit articular chondrocytes and in HIG-82 synovial cells

Intercellular communication through gap junctions allows tissue coordination of cell metabolism and sensitivity to extracellular stimuli, Intercellular Ca2+ signaling,vas investigated,vith digital fluorescence video imaging in primary cultures of articular chondrocytes and in HIG-82 synovial cells, In both cell types, mechanical stimulation of a single cell induced a wave of increased Ca2+ that was communicated to surrounding cells, Intercellular Ca2+ spreading was inhibited by 18 alpha-glycyrrhetinic acid, demonstrating the involvement of gap junctions in signal propagation, In the absence of extracellular Ca2+, mechanical stimulation induced communicated Ca2+ waves similar to controls; however, the number of HIG-82 cells recruited decreased significantly, Mechanical stress induced Ca2+ influx both in the stimulated chondrocyte and HIG-82 cell, but not in the adjacent cells, as assessed by the Mn2+ quenching technique, Treatment of cells with thapsigargin and with the phospholipase C (PLC) inhibitor U73122 blocked mechanically induced signal propagation, These results provide evidence that in chondrocytes and in HIG-82 synovial cells, mechanical stimulation activates PLC, thus leading to an increase of intracellular inositol 1,4,5-trisphosphate, The second messenger, by permeating gap junctions, stimulates intracellular Ca2+ release in neighboring cells, It is concluded that intercellular Ca2+ waves may provide a mechanism to coordinate tissue responses in joint physiology.