Journal
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
Volume 74, Issue 1, Pages 44-49Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1271/bbb.90529
Keywords
cGMP; cGMP-dependent protein kinase II (cGK-II); transcriptional regulation; chondrogenesis
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
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The C-type natriuretic peptide/natriuretic peptide receptor-B/cGMP pathway plays an important role in the regulation of endochondral ossification. In chondrocytes, the physiological effect of cGMP is mediated primarily by the activation of cGMP-dependent protein kinase II (cGK-II). In this study, we investigated the transcriptional regulation of cGK-II in chondrocytes. The expression pattern of cGK-II transcripts was examined during chondrogenic differentiation of ATDC5 cells. cGK-II mRNA was not detectable in undifferentiated cells, but increased dramatically prior to differentiation to the hypertrophic stage. To analyze the transcriptional regulation of cGK-II, the 5'-flanking region of the mouse cGK-II gene was isolated and characterized. The promoter activity of the cGK-II gene decreased markedly following deletion and mutagenesis of the putative Nkx-binding site between nucleotide positions -292 and -286. These results suggest that the homeobox gene Nkx family is critical for the transcriptional regulation of cGK-II during chondrogenesis.
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