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NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts
Odgren Lab Publications
  • Ricardo A. Battaglino, The Forsyth Institute
  • L. Pham, Forsyth Institute
  • Leslie R. Morse, Harvard University School of Medicine
  • M. Vokes, Forsyth Institute
  • A. Sharma, Forsyth Institute
  • Paul R. Odgren, University of Massachusetts Medical School
  • Meilheng Yang, University of Massachusetts Medical School
  • Hajime Sasaki, The Forsyth Institute
  • Philip Stashenko, The Forsyth Institute
UMMS Affiliation
Department of Cell Biology
Publication Date
Document Type
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

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.

DOI of Published Version
Bone. 2008 Jan;42(1):180-92. Epub 2007 Sep 26. Link to article on publisher's site
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Link to Article in PubMed
PubMed ID
Citation Information
Ricardo A. Battaglino, L. Pham, Leslie R. Morse, M. Vokes, et al.. "NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts" Vol. 42 Iss. 1 (2008) ISSN: 1873-2763 (Linking)
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