Changes in intracellular calcium concentration in response to hypertonicity in bovine articular chondrocytes

Sánchez, Julio César; Wilkins, Robert J.

doi:10.1016/j.cbpb.2003.09.025

Cited by 46 publications

(55 citation statements)

References 39 publications

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“…6), thus adding to the pleiotropic effects of hypertonicity on intracellular signaling (15). It has been reported that hypertonicity can increase intracellular calcium concentration (8,24,36,38). Therefore, it is possible that hypertonicity regulates the calcineurin-NFATc pathway through its effect on intracellular calcium level, independent of TonEBP/NFAT5 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Li¹,

McDill²,

Kovach³

et al. 2007

American Journal of Physiology-Cell Physiology

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December 13, 2006; doi:10.1152/ajpcell.00588.2005.-The aquaporin (AQP)2 channel mediates the reabsorption of water in renal collecting ducts in response to arginine vasopressin (AVP) and hypertonicity. Here we show that AQP2 expression is induced not only by the tonicityresponsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5-mediated hypertonic stress response but also by the calcium-dependent calcineurin-NFATc pathway. The induction of AQP2 expression by the calcineurin-NFATc pathway can occur in the absence of TonEBP/NFAT5. Mutational and chromatin immunoprecipitation analyses revealed the existence of functional NFAT binding sites within the proximal AQP2 promoter responsible for regulation of AQP2 by NFATc proteins and TonEBP/NFAT5. Contrary to the notion that TonEBP/NFAT5 is the only Rel/NFAT family member regulated by tonicity, we found that hypertonicity promotes the nuclear translocation of NFATc proteins for the subsequent induction of AQP2 expression. Calcineurin activity was also found to be involved in the induction of TonEBP/NFAT5 expression by hypertonicity, thus further defining the signaling mechanisms that underlie the TonEBP/NFAT5 osmotic stress response pathway. The coordinate regulation of AQP2 expression by both osmotic stress and calcium signaling appears to provide a means to integrate diverse extracellular signals into optimal cellular responses. aquaporin; nuclear factor of activated T cells; tonicity-responsive enhancer binding protein; osmotic response CELLS OF THE RENAL MEDULLA exist in a unique tissue environment characterized by extremes of hypertonicity during periods of antidiuresis, which allows for the efficient reabsorption of water from the glomerular filtrate (3). The hypertonic interstitial environment allows water to diffuse through the tubular epithelial cell membrane via aquaporin (AQP) water channels. Genetic studies in both mice and humans indicate that multiple AQPs, including AQP2, play a critical role in water transport in the kidney (21). AQP2 is expressed in cells of the renal collecting ducts that are exposed to the potentially hypertonic environment. Binding of arginine vasopressin (AVP) to AVP receptor 2 (AVPR2) induces the translocation of AQP2 from storage vesicles to the plasma membrane (21). Mutations in components of this pathway, especially in AVPR2 and AQP2, cause defects in urine concentration manifested as nephrogenic diabetes insipidus (NDI) (23). While AVP/AVPR2 signaling can regulate the long-term expression of AQP2 (35), regulation of AQP2 by AVP-independent mechanisms has also been reported (14,20,42).Although the hypertonic environment within the kidney allows for reabsorption of water, it also subjects cells to a potentially lethal osmotic stress. The cellular response that permits cells of the renal medulla to adapt and survive within a hypertonic environment is mediated by the tonicity-responsive enhancer binding protein (TonEBP)/nuclear factor of activated T cells (NFAT)5 transcription factor (13). TonEBP/ NF...

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Section: Discussionmentioning

confidence: 99%

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Li¹,

McDill²,

Kovach³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…Systems that import HCO À 3 ions play little or no role [37, 119], perhaps, because anions are to some extent excluded from the extracellular matrix, but most probably because levels of carbonic anhydrase expression are very low in chondrocytes [103]. As for other cells, Ca 2+ levels are determined by the balance of influx (leak through channels) and efflux (mediated in large part by Na + -Ca 2+ exchange, NCE) across the cell membrane, and by the exchange of Ca 2+ between the cytosol and intracellular stores [12,82,88,89,92].…”

Section: Ion Homeostasis In Articular Chondrocytesmentioning

confidence: 99%

Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis

Gibson

Milner

White

et al. 2007

Pflugers Arch - Eur J Physiol

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“…[10][11][12][13] Calcium is an ubiquitous second messenger which regulates many cellular processes including metabolism, proliferation, gene transcription, contraction, and mechanotransduction. 14 Previous studies have suggested that Ca 2þ signals form part of an intricate mechanotransduction pathway in chondrocytes: physical stimuli, such as compression, [15][16][17][18][19] fluid flow, [20][21][22] hydrostatic pressure, 23,24 and osmotic stress, [25][26][27][28][29] influence Ca 2þ signaling in chondrocytes. Therefore, insight into mechanically induced Ca 2þ signaling may provide novel understanding of chondrocyte mechanotransduction.…”

mentioning

confidence: 99%

Mechanically induced calcium signaling in chondrocytes in situ

Han

Wouters

Clark

2011

Journal Orthopaedic Research

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Changes in intracellular calcium (Ca 2þ ) concentration, also known as Ca 2þ signaling, have been widely studied in articular cartilage chondrocytes to investigate pathways of mechanotransduction. Various physical stimuli can generate an influx of Ca 2þ into the cell, which in turn is thought to trigger a range of metabolic and signaling processes. In contrast to most studies, the approach used in this study allows for continuous real time recording of calcium signals in chondrocytes in their native environment. Therefore, interactions of cells with the extracellular matrix (ECM) are fully accounted for. Calcium signaling was quantified for dynamic loading conditions and at different temperatures. Peak magnitudes of calcium signals were greater and of shorter duration at 378C than at 218C. Furthermore, Ca 2þ signals were involved in a greater percentage of cells in the dynamic compared to the relaxation phases of loading. In contrast to the time-delayed signaling observed in isolated chondrocytes seeded in agarose gel, Ca 2þ signaling in situ is virtually instantaneous in response to dynamic loading. These differences between in situ and in vitro cell signaling responses might provide crucial insight into the role of the ECM in providing pathways of mechanotransduction in the intact cartilage that are absent in isolated cells seeded in gel constructs.

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Changes in intracellular calcium concentration in response to hypertonicity in bovine articular chondrocytes

Cited by 46 publications

References 39 publications

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress

Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis

Mechanically induced calcium signaling in chondrocytes in situ

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