Regulation of sodium-dependent phosphate transport in osteoclasts.

Gupta, Arun; Guo, Xiao; Alvarez, Ulises; Hruska, Keith A.

doi:10.1172/jci119563

Cited by 51 publications

(67 citation statements)

References 34 publications

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“…Osteoclastogenesis was also evaluated in two experiments from primary rat bone marrow monocyte (BMM) cultures, as described previously (18,19) with modifications. All procedures concerning animal experiments were performed according to the Guidelines for the Care and Use of Animals available on the National Academies Press Web site.…”

Section: Methodsmentioning

confidence: 99%

Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss

Bársony

Sugimura

Verbalis

2011

Journal of Biological Chemistry

156

146

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Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis that is associated with increased osteoclast numbers in a rat model of the human disease of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We used cellular and molecular approaches to demonstrate that sustained low extracellular sodium ion concentrations ( Hyponatremia, defined as serum sodium ion concentration ([Na ϩ ]) less than 135 mmol/liter, is a frequently encountered electrolyte abnormality in patients. Chronic hyponatremia is an especially common disorder in elderly people, often due to the dysregulation of hypothalamic osmoregulatory mechanisms, leading to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).2 Hyponatremia may also arise from chronic heart failure or cirrhosis and from treatment with a large number of drugs, including diuretics and selective serotonin reuptake inhibitors. The estimated prevalence of chronic hyponatremia in the United States is in the range of 3.2-6.1 million persons annually, 75-80% of whom are without obvious neurological symptoms. Although chronic hyponatremia is often considered to be "asymptomatic," recent reports have shown its adverse effects, namely impaired gait stability and neurocognitive functions and, therefore, a greater risk of falls and fractures. In one recent case-controlled study of asymptomatic chronic hyponatremic patients, even mild hyponatremia was associated with a 67-fold increased odds ratio for falling compared with normonatremic controls. Even more alarming, a recent study from Belgium found that mild asymptomatic hyponatremia was associated with bone fractures in ambulatory elderly subjects (adjusted odds ratio of 4.16, 95% confidence interval: 2.24 -7.71) (1), and the incidence of hyponatremia in patients aged 65 or older with skeletal fractures was more than double that of patients with no fracture (9.1 and 4.1%, respectively; p ϭ 0.007) (2). Recent studies from our laboratory have indicated that hyponatremia is also associated with osteoporosis due to increased osteoclastic bone resorption in a rat model of SIADH (3). Histomorphometric analysis indicated that osteoclast number was increased 5-10-fold in excised femurs, tibia, and spine from hyponatremic rats, and analysis of blood samples revealed no significant metabolic or hormonal change that could account for the increased osteoclastic bone resorption (3). Early studies of radionucleotide distribution indicated that approximately one-third of the body's sodium is stored in the bone matrix along with calcium and phosphorus and is released during osteoclastic resorption (4). A more recent study has also shown that large amounts of sodium are stored in an osmotically inactive compartment in the bones of dogs and are released from this store during prolonged dietary sodium deprivation (5). The primary components of bone matrix are removed by osteoclasts first by demineralization of the inorganic mineral through acidification of the...

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Section: Methodsmentioning

confidence: 99%

Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss

Bársony

Sugimura

Verbalis

2011

Journal of Biological Chemistry

156

146

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“…This is achieved largely by a control of the renal capacity to reabsorb P i from the primary urine and, to a lesser extent, by a control of small intestinal absorption of P i (see below). Expression of SLC34 members was also described in other tissues such as bone [13], brain [17], mammary glands [31], and lung [8,41] (Fig. 2); however, the physiological roles of type ll Na/P i -cotransporters described at these sites have not yet been entirely defined.…”

Section: Physiological Pathological and Pharmaceutical Aspectsmentioning

confidence: 97%

The sodium phosphate cotransporter family SLC34

Murer

Forster

Biber

2004

Pfl�gers Archiv European Journal of Physiology

281

234

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This review summarizes the characteristics of the solute carrier family SLC34 that is represented by the type ll Na/P(i)-cotransporters NaPi-lla (SLC34A1), NaPi-llb (SLC34A2) and NaPi-llc (SLC34A3). Other Na/P(i)-cotransporters are described within the SLC17 and SLC20 families. Type ll Na/P(i)-cotransporters are expressed in several tissues and play a major role in the homeostasis of inorganic phosphate. In kidney and small intestine, type ll Na/P(i)-cotransporters are located at the apical sites of epithelial cells and represent the rate limiting steps for transepithelial movement of phosphate. Physiological and pathophysiological regulation of renal and small intestinal epithelial transport of phosphate occurs through alterations in the abundance of type ll Na/P(i)-cotransporters.

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“…As demonstrated recently by targeted inactivation, the type II Na͞P i -cotransporter represents the major pathway by which P i is reabsorbed (1,2). With the exception of osteoclasts (3), expression of the type II cotransporter has not yet been described other than in proximal tubules.…”

mentioning

confidence: 99%

Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine

Hilfiker

Hattenhauer

Traebert

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

333

309

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An isoform of the mammalian renal type II Na͞P i -cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na͞P i -cotransporter. Na͞P i -cotransport mediated by the type IIb cotransporter was studied in oocytes of Xenopus laevis. The results indicate that type IIb Na͞P i -cotransport is electrogenic and in contrast to the renal type II isoform of opposite pH dependence. Expression of type IIb mRNA was detected in various tissues, including small intestine. The type IIb protein was detected as a 108-kDa protein by Western blots using isolated small intestinal brush border membranes and by immunohistochemistry was localized at the luminal membrane of mouse enterocytes. Expression of the type IIb protein in the brush borders of enterocytes and transport characteristics suggest that the described type IIb Na͞P i -cotransporter represents a candidate for small intestinal apical Na͞P icotransport.

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Regulation of sodium-dependent phosphate transport in osteoclasts.

Cited by 51 publications

References 34 publications

Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss

Osteoclast Response to Low Extracellular Sodium and the Mechanism of Hyponatremia-induced Bone Loss

The sodium phosphate cotransporter family SLC34

Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine

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