Transcriptional regulation of cGMP-dependent protein kinase 2 (cGK-2) in chondrocytes

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  • YUASA Keizo
    Department of Biological Science and Technology, The University of Tokushima Graduate School
  • UEHARA Shotaro
    Department of Biological Science and Technology, The University of Tokushima Graduate School
  • NAGAHAMA Masami
    Department of Biological Science and Technology, The University of Tokushima Graduate School
  • TSUJI Akihiko
    Department of Biological Science and Technology, The University of Tokushima Graduate School

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  • Transcriptional Regulation of cGMP-Dependent Protein Kinase II (cGK-II) in Chondrocytes

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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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