Cbfa1 isoforms exert functional differences in osteoblast differentiation.

作者: Hideyuki Harada , Shuzo Tagashira , Masanori Fujiwara , Shinji Ogawa , Takashi Katsumata

DOI: 10.1074/JBC.274.11.6972

关键词:

摘要: Cbfa1 is an essential transcription factor for osteoblast differentiation and bone formation. We investigated functional differences among three isoforms of Cbfa1: Type I (originally reported as Pebp2alphaA by Ogawa et al. (Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, Lu, J., Satake, Shigesada, K., Ito, Y. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6859-6863), II til-1 Stewart (Stewart, Terry, A., Hu, O'Hara, Blyth, Baxter, Cameron, Onions, D. Neil, J. C. (1997) 94, 8646-8651), III Osf2/Cbfa1 Ducy (Ducy, P., Zhang, R., Geoffroy, V., Ridall, L., Karsenty, G. Cell 89, 747-754). A reverse transcriptase-polymerase chain reaction analysis demonstrated that these were expressed in adult mouse bones. The transient transfection or a fibroblastic cell line, C3H10T1/2, induced the expression alkaline phosphatase (ALP) activity. This induction was synergistically enhanced co-introduction Xenopus BMP-4 cDNA. In contrast, cDNA no ALP C3H10T1/2 cells stably transfected with each isoform Cbfa1, gene also strongly but not Cbfa1. Osteocalcin, osteopontin,and type collagen expressions up-regulated all exhibited highest level osteocalcin gene. luciferase reporter assay using 6XOSE2-SV40 promoter (6 tandem binding elements ligated front SV40 sequence), promoter, osteopontin revealed transcriptional target genes without its beta-subunit. These results suggest used present study are involved stimulatory action differentiation, they exert different functions process differentiation.

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