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dc.contributor.authorAitken, CJ
dc.contributor.authorHodge, JM
dc.contributor.authorNishinaka, Y
dc.contributor.authorVaughan, T
dc.contributor.authorYodoi, JJ
dc.contributor.authorDay, CJ
dc.contributor.authorMorrison, NA
dc.contributor.authorNicholson, GC
dc.date.accessioned2017-05-03T11:03:12Z
dc.date.available2017-05-03T11:03:12Z
dc.date.issued2004
dc.date.modified2009-09-03T07:16:21Z
dc.identifier.issn0884-0431
dc.identifier.doi10.1359/JBMR.040913
dc.identifier.urihttp://hdl.handle.net/10072/5641
dc.description.abstractDifferential expression of TBP-2 and Trx-1 occurs during osteoclastogenesis. Adenoviral overexpression of TBP-2 in osteoclast precursors inhibits Trx-1 expression, osteoclast formation, and AP-1 binding activity. TBP-2 and Trx-1 are key regulators of osteoclastogenesis. Introduction: Thioredoxin binding protein-2 (TBP-2) negatively regulates thioredoxin-1 (Trx-1), a key endogenous modulator of cellular redox and signaling. In gene array analysis, we found that TBP-2 expression was reduced during human osteoclast differentiation compared with macrophage differentiation. Our aim was to determine the roles of TBP-2 and Trx-1 in human osteoclastogenesis and RANKL signaling. Materials and Methods: Osteoclasts or macrophages were generated from colony-forming unit-granulocyte macrophage (CFU-GM) precursors treated with sRANKL and macrophage-colony-stimulating factor (M-CSF), or M-CSF alone, respectively. Expression of TBP-2 and Trx-1 was quantified by real-time PCR and Western analysis. Adenoviral gene transfer was used to overexpress TBP-2 in precursors. NF-?B and activator protein 1 (AP-1) signaling was assessed with EMSA. Results: In the presence of sRANKL, expression of TBP-2 was decreased, whereas Trx-1 expression was increased. The antioxidant N-acetylcysteine reversed this pattern and markedly inhibited osteoclastogenesis. Adenoviral overexpression of human TBP-2 in precursors inhibited osteoclastogenesis and Trx-1 expression, inhibited sRANKL-induced DNA binding of AP-1, but enhanced sRANKL-induced DNA binding of NF-?B. Conclusions: These data support significant roles for TBP-2 and the Trx system in osteoclast differentiation that are mediated by redox regulation of AP-1 transcription. A likely mechanism of stress signal induction of bone resorption is provided. Modulators of the Trx system such as antioxidants have potential as antiresorptive therapies.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_AU
dc.publisherAmerican Society for Bone and Mineral Research
dc.publisher.placeWashington
dc.publisher.urihttp://www.jbmronline.org/loi/jbmr
dc.relation.ispartofpagefrom2057
dc.relation.ispartofpageto2064
dc.relation.ispartofissue12
dc.relation.ispartofjournalJournal of Bone and Mineral Research
dc.relation.ispartofvolume19
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchEngineering
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode09
dc.subject.fieldofresearchcode11
dc.titleRegulation of Human Osteoclast Differentiation by Thioredoxin Binding Protein-2 and Redox-Sensitive Signaling.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2004
gro.hasfulltextNo Full Text
gro.griffith.authorMorrison, Nigel A.
gro.griffith.authorVaughan, Tanya
gro.griffith.authorDay, Christopher J.


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