NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts
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AuthorsBattaglino, Ricardo A.
Morse, Leslie R.
Odgren, Paul R.
UMass Chan AffiliationsDepartment of Cell Biology
Document TypeJournal Article
KeywordsAmino Acid Sequence
Gene Expression Regulation
Molecular Sequence Data
RNA, Small Interfering
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AbstractBone resorption is regulated by a complex system of hormones and cytokines that cause osteoblasts/stromal cells and lymphocytes to produce factors including RANKL, that ultimately result in the differentiation and activation of osteoclasts, the bone resorbing cells. We used a microarray approach to identify genes upregulated in RANKL-stimulated osteoclast precursor cells. Osteoclast expression was confirmed by multiple tissue Northern and in situ hybridization analysis. Gene function studies were carried out by siRNA analysis. We identified a novel gene, which we termed nha-oc/NHA2, which is strongly upregulated during RANKL-induced osteoclast differentiation in vitro and in vivo. nha-oc/NHA2 encodes a novel cation-proton antiporter (CPA) and is the mouse orthologue of a human gene identified in a database search: HsNHA2. nha-oc/NHA2 is selectively expressed in osteoclasts. NHA-oc/NHA2 protein localizes to the mitochondria, where it mediates Na(+)-dependent changes in mitochondrial pH and Na(+) acetate induced mitochondrial passive swelling. RNA silencing of nha-oc/nha2 reduces osteoclast differentiation and resorption, suggesting a role for NHA-oc/NHA2 in these processes. nha-oc/NHA2 therefore is a novel member of the CPA family and is the first mitochondrial NHA characterized to date. nha-oc/NHA2 is also unique in that it is the first eukaryotic and tissue-specific CPA2 characterized to date. NHA-oc/NHA2 displays the expected activities of a bona fide CPA and plays a key role(s) in normal osteoclast differentiation and function.
SourceBone. 2008 Jan;42(1):180-92. Epub 2007 Sep 26. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42877
Related ResourcesLink to Article in PubMed