Skip to main content
Article
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
Date
1-9-2008
Document Type
Article
Medical Subject Headings
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
Disciplines
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.
Rights and Permissions
Citation: Bone. 2008 Jan;42(1):180-92. Epub 2007 Sep 26. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
17988971
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)
Available at: http://works.bepress.com/paul_odgren/4/