Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect of thiazide diuretics

The use of thiazide diuretics is associated with increased bone mineral density and, in some studies with reduced incidence of fractures, suggesting a potential role for these drugs in the treatment of osteoporosis. Our objective was to examine the effects of thiazides on osteoblast-like cells using the rat UMR-106 osteosarcoma cell line. Treatment of UMR-106 cells with chlorothiazide caused membrane depolarization and a rise of intracellular calcium but had no effect on adenosine 3,5'-cyclic monophosphate accumulation. The rise of intracellular calcium was partially inhibited by nifedipine and removal of extracellular calcium, indicating calcium uptake from the extracellular media, as well as by thapsigargin or dantrolene, indicating contributions from calcium release from intracellular stores. Reverse transcriptase-polymerase chain reaction was used to isolate a partial cDNA clone for the thiazide-sensitive sodium-chloride cotransporter from UMR-106 cells that hybridized to 5.0- and 11.0-kilobase mRNAs when Northern blot analysis was conducted. Antisense oligonucleotides to the sodium-chloride cotransporter specifically inhibited the chlorothiazide-induced depolarization and rise of intracellular calcium and reduced immunofluorescence staining for the sodium-chloride cotransporter protein in UMR-106 cells. We conclude that thiazide diuretics inhibit sodium-chloride cotransporter activity in UMR-106 cells, thereby altering intracellular calcium regulation. These results provide evidence for direct effects of thiazide diuretics on bone cells.

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Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.253.1.e45 ◽

1987 ◽

Vol 253 (1) ◽

pp. E45-E51 ◽

Cited By ~ 4

Author(s):

I. R. Reid ◽

R. Civitelli ◽

L. R. Halstead ◽

L. V. Avioli ◽

K. A. Hruska

Keyword(s):

Parathyroid Hormone ◽

Intracellular Calcium ◽

Calcium Concentration ◽

Calcium Transient ◽

Peak Height ◽

Base Line ◽

Osteosarcoma Cell ◽

Cellular Processes ◽

Osteoblastic Phenotype ◽

Umr 106

Changes in cytoplasmic calcium concentration ([Ca2+]i) activate numerous cellular processes thus mediating the effects of a number of hormones, but whether this mechanism is involved in the activation of osteoblasts by parathyroid hormone (PTH) remains uncertain. To examine this question, [Ca2+]i has been measured in suspensions of UMR 106 cells, a rodent osteosarcoma cell line with an osteoblastic phenotype. Basal [Ca2+]i was 137 +/- 3.7 nM (n = 60) and after the addition of rat PTH-(1–34) [rPTH-(1-34)] there was a rapid, dose-related increase with return to base line within 1 min. Half-maximal stimulation was produced by 5 X 10(-8) M rPTH-(1-34). Complexing of intracellular calcium by EGTA addition immediately before that of rPTH did not affect the calcium transient; neither did MnCl2 (10(-4) M) nor diltiazem (10(-4) M). Verapamil (10(-5) M) reduced the [Ca2+]i peak height after rPTH to 0.48 +/- 0.14 of control (n = 7). 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoic acid and dantrolene both reduced the [Ca2+]i response to rPTH (0.65 +/- 0.08 and 0.29 +/- 0.13 of control, respectively). Forskolin (10(-6) and 10(-5) M) produced a slight [Ca2+]i transient smaller in amplitude than seen with PTH. It is concluded that PTH mobilizes an intracellular calcium pool in these osteoblastlike cells, and the predominant mechanism for this is independent of cAMP.

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Regulation of intracellular calcium release during fertilization in sea urchin eggs

10.31274/rtd-180813-13280 ◽

1997 ◽

Author(s):

Shyh-Jye Lee

Keyword(s):

Intracellular Calcium ◽

Sea Urchin ◽

Calcium Release ◽

Sea Urchin Eggs ◽

Intracellular Calcium Release

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Faculty Opinions recommendation of Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1001269.37056 ◽

2002 ◽

Author(s):

Marcus Thelen

Keyword(s):

Intracellular Calcium ◽

Calcium Release ◽

Calcium Influx ◽

Extracellular Calcium ◽

Bacterial Clearance ◽

Cyclic Adp Ribose ◽

Intracellular Calcium Release

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Faculty Opinions recommendation of The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13352994.792002904 ◽

2012 ◽

Author(s):

Paul Sanders

Keyword(s):

Sodium Chloride ◽

Calcineurin Inhibitor ◽

Sodium Chloride Cotransporter

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Protein kinase C-activated calcium channel in the osteoblast-like clonal osteosarcoma cell line UMR-106.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)48123-9 ◽

1987 ◽

Vol 262 (31) ◽

pp. 14967-14973 ◽

Cited By ~ 5

Author(s):

D T Yamaguchi ◽

C R Kleeman ◽

S Muallem

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Calcium Channel ◽

Cell Line ◽

Osteosarcoma Cell Line ◽

Osteosarcoma Cell ◽

Kinase C ◽

Umr 106

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Orientia tsutsugamushi Inhibits Apoptosis of Macrophages by Retarding Intracellular Calcium Release

Infection and Immunity ◽

10.1128/iai.70.8.4692-4696.2002 ◽

2002 ◽

Vol 70 (8) ◽

pp. 4692-4696 ◽

Cited By ~ 16

Author(s):

Mee-Kyung Kim ◽

Seung-Yong Seong ◽

Ju-Young Seoh ◽

Tae-Hee Han ◽

Hyeon-Je Song ◽

...

Keyword(s):

Intracellular Calcium ◽

Calcium Concentration ◽

Calcium Release ◽

Cytosolic Calcium ◽

Orientia Tsutsugamushi ◽

Cytosolic Calcium Concentration ◽

Infected Cells ◽

Intracellular Calcium Release ◽

Calcium Redistribution ◽

In Cells

ABSTRACT Orientia tsutsugamushi shows both pro- and antiapoptotic activities in infected vertebrate cells. Apoptosis of THP-1 cells induced by beauvericin was inhibited by O. tsutsugamushi infection. Beauvericin-induced calcium redistribution was significantly reduced and retarded in cells infected with O. tsutsugamushi. Antiapoptotic activities of O. tsutsugamushi in infected cells are most probably due to inhibition of the increase in the cytosolic calcium concentration.

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Aging and the Osteogenic Response to Mechanical Loading

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.11.s1.s137 ◽

2001 ◽

Vol 11 (s1) ◽

pp. S137-S142 ◽

Cited By ~ 26

Author(s):

Wendy M. Kohrt

Keyword(s):

Growth Factors ◽

Bone Mass ◽

Mechanical Loading ◽

Bone Cells ◽

Weight Bearing ◽

Bone Modeling ◽

Mineral Density ◽

Increase Bone Mass ◽

Age Related ◽

Osteogenic Response

The osteogenic response to mechanical stress is blunted with aging. It has been postulated that this decline in responsiveness is related to (a) a limited ability to engender the strain necessary to reach the bone modeling threshold, due to decreased muscle mass and strength, and/or (b) a decline in certain hormones or growth factors that may interact with mechanical signals to change the sensitivity of bone cells to strain. There is reason to believe that both of these factors contribute to the reduced ability to increase bone mass through exercise with advancing age. Weight-bearing endurance exercise and resistance exercise have both been found to increase bone mass in older women and men. However, exercise training studies involving older individuals have generally resulted in increased bone mineral density only when the exercise is quite vigorous. There is also evidence that the osteogenic response to mechanical loading is enhanced by estrogens. Whether age-related changes in other factors (e.g., other hormones, growth factors, cytokines) also contribute to the reduced responsiveness of the aged skeleton to mechanical loading remains to be investigated.

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A SIMPLE MODEL FOR INTERACTION OF VOLTAGE AND CALCIUM DYNAMICS IN VIRTUAL VENTRICULAR TISSUE

International Journal of Bifurcation and Chaos ◽

10.1142/s0218127403008776 ◽

2003 ◽

Vol 13 (12) ◽

pp. 3873-3886

Author(s):

O. V. ASLANIDI ◽

A. V. HOLDEN

Keyword(s):

Intracellular Calcium ◽

Calcium Release ◽

Cell Model ◽

Excitation Threshold ◽

Calcium Dynamics ◽

Variable Model ◽

Ventricular Cell ◽

Calcium Dependent ◽

Intracellular Ca ◽

A Site

A simple two-variable model is used to replace the formulation of calcium dynamics in the Luo–Rudy ventricular cell model. Virtual ventricular cell and tissue are developed and validated to reproduce restitution properties and calcium-dependent voltage patterns present in the original model. Basic interactions between the membrane potential and Ca 2+ dynamics in the virtual cell and a strand of the virtual tissue are studied. Intracellular calcium waves can be linked to both action potentials (APs) and delayed afterdepolarizations (DADs). An intracellular calcium wave propagating from the cell interior can induce an AP upon reaching the cell membrane. The voltage and the intracellular Ca 2+ patterns within the same cell can be highly desynchronized. In a one-dimensional strand of the virtual tissue calcium motion is driven by the AP propagation. However, calcium release can be induced upon certain conditions (e.g. Na + overload of the cells), which results in DADs propagating in the wake of AP. Such propagating DADs can reach the excitation threshold, generating a pair of extrasystolic APs. Collision of a propagating AP with a site of elevated intracellular Ca 2+ concentration does not affect the propagation under the normal conditions. Under Na + overload local elevation of the intracellular Ca 2+ leads to generation of an extrasystolic AP, which destroys the original propagating AP.

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