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 was investigated with 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 18alpha-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.
Grandolfo
M
M
Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, Università di Trieste, Italy.
Calabrese
A
A
D'Andrea
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism*; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism*; D003470:Culture Media / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D016257:Fura-2; D017629:Gap Junctions / Q000378:metabolism; D010812:Physical Stimulation; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D003470:Culture Media; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2