TY - JOUR
T1 - Mechanisms contributing to fluid-flow-induced Ca2+ mobilization in articular chondrocytes
AU - Yellowley-genetos, Clare E
AU - Jacobs, Christopher R.
AU - Donahue, Henry J.
PY - 1999
Y1 - 1999
N2 - We previously showed that fluid flow, which chondrocytes experience in vivo and which results in a variety of morphological and metabolic changes in cultured articular chondrocytes, can also stimulate a rise in intracellular calcium concentration ([Ca2+](i)). However, the mechanism by which Ca2+ is mobilized in response to flow is unclear. In this study, we investigated the roles of intracellular Ca2+ stores, G-proteins, and extracellular ATP in the flow-induced Ca2+ response in bovine articular chondrocytes (BAC). Cells loaded with the Ca2+ sensitive dye Fura-2 were exposed to steady flow at 34 ml/min (37 dynes/cm2) in a parallel plate flow chamber. Whereas ryanodine and caffeine had no effect, both neomycin and thapsigargin significantly decreased the Ca2+(l) response to flow, suggesting a role for Ca2+ store release, possibly through an inositol 1,4,5-trisphosphate (IP3)-dependent mechanism. Twenty-four-hour treatment with pertussis toxin also significantly decreased the response, suggesting that the mechanism may be G-protein regulated. In addition, ATP release by chondrocytes does not appear to mediate the flow-induced Ca2+ response because suramin, a P2 purinergic blocker, had no effect. These results suggest that BAC respond rapidly to changes in their mechanical environment, such as increased fluid flow, by a mechanism that involves IP3 stimulated Ca2+(i) release and G- protein activation.
AB - We previously showed that fluid flow, which chondrocytes experience in vivo and which results in a variety of morphological and metabolic changes in cultured articular chondrocytes, can also stimulate a rise in intracellular calcium concentration ([Ca2+](i)). However, the mechanism by which Ca2+ is mobilized in response to flow is unclear. In this study, we investigated the roles of intracellular Ca2+ stores, G-proteins, and extracellular ATP in the flow-induced Ca2+ response in bovine articular chondrocytes (BAC). Cells loaded with the Ca2+ sensitive dye Fura-2 were exposed to steady flow at 34 ml/min (37 dynes/cm2) in a parallel plate flow chamber. Whereas ryanodine and caffeine had no effect, both neomycin and thapsigargin significantly decreased the Ca2+(l) response to flow, suggesting a role for Ca2+ store release, possibly through an inositol 1,4,5-trisphosphate (IP3)-dependent mechanism. Twenty-four-hour treatment with pertussis toxin also significantly decreased the response, suggesting that the mechanism may be G-protein regulated. In addition, ATP release by chondrocytes does not appear to mediate the flow-induced Ca2+ response because suramin, a P2 purinergic blocker, had no effect. These results suggest that BAC respond rapidly to changes in their mechanical environment, such as increased fluid flow, by a mechanism that involves IP3 stimulated Ca2+(i) release and G- protein activation.
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U2 - 10.1002/(SICI)1097-4652(199909)180:3<402::AID-JCP11>3.0.CO;2-4
DO - 10.1002/(SICI)1097-4652(199909)180:3<402::AID-JCP11>3.0.CO;2-4
M3 - Article
C2 - 10430180
AN - SCOPUS:0032767329
VL - 180
SP - 402
EP - 408
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
IS - 3
ER -