HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/C526    most recent 00357.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Ito, M. Articles by Miyamoto, K.-i. Search for Related Content PubMed PubMed Citation Articles by Ito, M. Articles by Miyamoto, K.-i.

CELLULAR METABOLISM

Unique uptake and efflux systems of inorganic phosphate in osteoclast-like cells

¹Department of Molecular Nutrition and ²Project Team of the Human Nutritional Science on Stress Control 21st Century Center of Excellence Program, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

Submitted 27 June 2006 ; accepted in final form 16 August 2006

During bone resorption, a large amount of inorganic phosphate (P_i) is generated within the osteoclast hemivacuole. The mechanisms involved in the disposal of this P_i are not clear. In the present study, we investigated the efflux of P_i from osteoclast-like cells. P_i efflux was activated by acidic conditions in osteoclast-like cells derived by the treatment of RAW264.7 cells with receptor activator of nuclear factor-B ligand. Acid-induced P_i influx was not observed in renal proximal tubule-like opossum kidney cells, osteoblast-like MC3T3-E1 cells, or untreated RAW264.7 cells. Furthermore, P_i efflux was stimulated by extracellular P_i and several P_i analogs [phosphonoformic acid (PFA), phosphonoacetic acid, arsenate, and pyrophosphate]. P_i efflux was time dependent, with 50% released into the medium after 10 min. The efflux of P_i was increased by various inhibitors that block P_i uptake, and extracellular P_i did not affect the transport of [¹⁴C]PFA into the osteoclast-like cells. Preloading of cells with P_i did not stimulate P_i efflux by PFA, indicating that the effect of P_i was not due to transstimulation of P_i transport. P_i uptake was also enhanced under acidic conditions. Agents that prevent increases in cytosolic free Ca²⁺ concentration, including acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 2-aminoethoxydiphenyl borate, and bongkrekic acid, significantly inhibited P_i uptake in the osteoclast-like cells, suggesting that P_i uptake is regulated by Ca²⁺ signaling in the endoplasmic reticulum and mitochondria of osteoclast-like cells. These results suggest that osteoclast-like cells have a unique P_i uptake/efflux system and can prevent P_i accumulation within osteoclast hemivacuoles.

phosphate transporter; RAW264.7; proton dependent; acidification