ASBMR 25th Annual Meeting SU001-SU482

Autor: Damian E. Myers, Geoffrey C. Nicholson, Jason M. Hodge, Nigel Alexander Morrison, Tanya Vaughan, C. J. Aitken
Rok vydání: 2003
Předmět:
Zdroj: Journal of Bone and Mineral Research. 18:S175-S285
ISSN: 0884-0431
Popis: Using 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.
Databáze: OpenAIRE
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