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    NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts

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    Authors
    Battaglino, Ricardo A.
    Pham, L.
    Morse, Leslie R.
    Vokes, M.
    Sharma, A.
    Odgren, Paul R.
    Yang, Meilheng
    Sasaki, Hajime
    Stashenko, Philip
    UMass Chan Affiliations
    Department of Cell Biology
    Document Type
    Journal Article
    Publication Date
    2008-01-09
    Keywords
    Amino Acid Sequence
    Animals
    Antiporters
    Caspases
    Cell Differentiation
    Cell Line
    Cloning, Molecular
    Enzyme Activation
    Gene Expression Regulation
    Humans
    Hydrogen-Ion Concentration
    Mice
    Mitochondria
    Mitochondrial Swelling
    Molecular Sequence Data
    Osteoclasts
    RNA, Messenger
    RNA, Small Interfering
    Cell Biology
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    Link to Full Text
    http://dx.doi.org/10.1016/j.bone.2007.09.046
    Abstract
    Bone 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.
    Source
    Bone. 2008 Jan;42(1):180-92. Epub 2007 Sep 26. Link to article on publisher's site
    DOI
    10.1016/j.bone.2007.09.046
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/42877
    PubMed ID
    17988971
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bone.2007.09.046
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