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dc.contributor.authorAitken, C.en_US
dc.contributor.authorJM, Hodgeen_US
dc.contributor.authorVaughan, Tanyaen_US
dc.contributor.authorDE, Myersen_US
dc.contributor.authorMorrison, Nigelen_US
dc.contributor.authorNicholson, G.en_US
dc.description.abstractUsing gene array analysis, we found that thioredoxin (TRX) binding protein-2 (TBP-2) was down-regulated during osteoclast (OC) differentiation. TBP-2 is a negative regulator of TRX, a small protein with a redox-active dithiol active site. TRX enhances DNA binding of redox-sensitve transcription factors such as NF?B and AP-1. OC were generated on dentine slices using human CFU-GM precursor cells treated with RANKL and M-CSF. At 4 days of culture, efficient (>80%) infection with adenovirus expressing ߭galactosidase (AdLacZ) was achieved. Infection with adenovirus expressing TBP-2 (AdTBP-2) for 14 days resulted in 66% reduction in the total TRAP+ area and 50% reduction in OC numbers as compared to the AdLacZ control. The size of OC formed in the presence of AdTBP-2 was reduced by 66% and they contained fewer nuclei. Resorption of dentine was inhibited by 80%. In mature OC infected with AdTBP-2, RANKL-induced NF?B activation was reduced by 63% and Western analysis demonstrated markedly increased expression of TBP-2 protein. We have shown that the over-expression of TBP-2, a gene down-regulated during OC formation, inhibits OC differentiation and NF?B activation. These results are consistent with the known function of TBP-2 as a negative regulator of TRX and the importance of the redox-sensitive transcription factor NF?B in osteoclastogenesis.en_US
dc.publisherAmerican Society for Bone and Mineral Researchen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofconferencename25th Annual Meeting of the American Society for Bone and Mineral Researchen_US
dc.relation.ispartofconferencetitleJournal of Bone and Mineral Research 18: S226 Suppl. 1en_US
dc.relation.ispartoflocationMinneapolis, Minnesota, USAen_US
dc.titleOver-expression of TBP-2, a protein involved in redox regulation, inhibits osteoclastogenesis.en_US
dc.typeConference outputen_US
dc.type.descriptionE3 - Conference Publications (Extract Paper)en_US
dc.type.codeE - Conference Publicationsen_US
gro.hasfulltextNo Full Text

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