Mechanisms contributing to fluid-flow-induced Ca2+ mobilization in articular chondrocytes
✍ Scribed by Clare E. Yellowley; Christopher R. Jacobs; Henry J. Donahue
- Book ID
- 101260676
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 152 KB
- Volume
- 180
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 ([Ca 2ϩ ] i ). However, the mechanism by which Ca 2ϩ is mobilized in response to flow is unclear. In this study, we investigated the roles of intracellular Ca 2ϩ stores, G-proteins, and extracellular ATP in the flow-induced Ca 2ϩ response in bovine articular chondrocytes (BAC). Cells loaded with the Ca 2ϩ sensitive dye Fura-2 were exposed to steady flow at 34 ml/min (37 dynes/cm 2 ) in a parallel plate flow chamber. Whereas ryanodine and caffeine had no effect, both neomycin and thapsigargin significantly decreased the Ca 2ϩ i response to flow, suggesting a role for Ca 2ϩ store release, possibly through an inositol 1,4,5-trisphosphate (IP 3 )-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 Ca 2ϩ 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 IP 3 stimulated Ca 2ϩ i release and G-protein activation.