Sodium/hydrogen exchanger NHA2 in osteoclasts: subcellular localization and role in vitro and in vivo.

Details

Serval ID
serval:BIB_EDD41E59FB63
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sodium/hydrogen exchanger NHA2 in osteoclasts: subcellular localization and role in vitro and in vivo.
Journal
Bone
Author(s)
Hofstetter W., Siegrist M., Simonin A., Bonny O., Fuster D.G.
ISSN
1873-2763[electronic], 1873-2763[linking]
Publication state
Published
Issued date
2010
Volume
47
Number
2
Pages
331-340
Language
english
Abstract
NHA2 was recently identified as a novel sodium/hydrogen exchanger which is strongly upregulated during RANKL-induced osteoclast differentiation. Previous in vitro studies suggested that NHA2 is a mitochondrial transporter required for osteoclast differentiation and bone resorption. Due to the lack of suitable antibodies, NHA2 was studied only on RNA level thus far. To define the protein's role in osteoclasts in vitro and in vivo, we generated NHA2-deficient mice and raised several specific NHA2 antibodies. By confocal microscopy and subcellular fractionation studies, NHA2 was found to co-localize with the late endosomal and lysosomal marker LAMP1 and the V-ATPase a3 subunit, but not with mitochondrial markers. Immunofluorescence studies and surface biotinylation experiments further revealed that NHA2 was highly enriched in the plasma membrane of osteoclasts, localizing to the basolateral membrane of polarized osteoclasts. Despite strong upregulation of NHA2 during RANKL-induced osteoclast differentiation, however, structural parameters of bone, quantified by high-resolution microcomputed tomography, were not different in NHA2-deficient mice compared to wild-type littermates. In addition, in vitro RANKL stimulation of bone marrow cells isolated from wild-type and NHA2-deficient mice yielded no differences in osteoclast development and activity. Taken together, we show that NHA2 is a RANKL-induced plasmalemmal sodium/hydrogen exchanger in osteoclasts. However, our data from NHA2-deficient mice suggest that NHA2 is dispensable for osteoclast differentiation and bone resorption both in vitro and in vivo.
Keywords
Animals, Antiporters/deficiency, Antiporters/metabolism, Bone and Bones/cytology, Bone and Bones/radiography, Cell Differentiation, Cell Line, Cell Membrane/metabolism, Cell Polarity, Mice, Mice, Transgenic, Osteoclasts/cytology, Osteoclasts/metabolism, Phenotype, Protein Transport, Subcellular Fractions/metabolism, X-Ray Microtomography
Pubmed
Web of science
Create date
31/01/2011 11:32
Last modification date
20/08/2019 17:15
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