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dc.contributor.authorBattaglino, Ricardo A.
dc.contributor.authorPham, L.
dc.contributor.authorMorse, Leslie R.
dc.contributor.authorVokes, M.
dc.contributor.authorSharma, A.
dc.contributor.authorOdgren, Paul R.
dc.contributor.authorYang, Meilheng
dc.contributor.authorSasaki, Hajime
dc.contributor.authorStashenko, Philip
dc.date2022-08-11T08:10:07.000
dc.date.accessioned2022-08-23T16:56:12Z
dc.date.available2022-08-23T16:56:12Z
dc.date.issued2008-01-09
dc.date.submitted2011-02-16
dc.identifier.citationBone. 2008 Jan;42(1):180-92. Epub 2007 Sep 26. <a href="http://dx.doi.org/10.1016/j.bone.2007.09.046">Link to article on publisher's site</a>
dc.identifier.issn1873-2763 (Linking)
dc.identifier.doi10.1016/j.bone.2007.09.046
dc.identifier.pmid17988971
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42877
dc.description.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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17988971&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.bone.2007.09.046
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectAntiporters
dc.subjectCaspases
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectCloning, Molecular
dc.subjectEnzyme Activation
dc.subjectGene Expression Regulation
dc.subjectHumans
dc.subjectHydrogen-Ion Concentration
dc.subjectMice
dc.subjectMitochondria
dc.subjectMitochondrial Swelling
dc.subjectMolecular Sequence Data
dc.subjectOsteoclasts
dc.subjectRNA, Messenger
dc.subjectRNA, Small Interfering
dc.subjectCell Biology
dc.titleNHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts
dc.typeJournal Article
dc.source.journaltitleBone
dc.source.volume42
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/odgren/6
dc.identifier.contextkey1789901
html.description.abstract<p>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.</p>
dc.identifier.submissionpathodgren/6
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages180-92


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