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KMID : 0381120090310030261
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Genes and Genomics
2009 Volume.31 No. 3 p.261 ~ p.266
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Modulation of Osteocalcin Expression by Purmorphamine Derivatives
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Kim Hye-Ryun
Jeong So-Hee
Im Young-Sam
Cho Sung-Yun
Choi Joong-Kwon
Shin Hea-Kyeong
Kim Yong-Min
Song Jin-Ook
Jeon Seong-Ho
Choi Joong-Kook
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Abstract
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Purmorphamine is a purine analog and it affects osteogenesis, in part, through the modulation of Sonic Hedgehog signaling pathway. However, the underlying mechanism has remained elusive. Previously, we identified two purmorphamine derivatives that modulate the expression of osteogenic markers including Runx2, Dlx2 and Hes1. However, the extents of osteogenesis varied depending on the assay employed, and this necessitates the identification of reliable markers. Here, we report that the expression of osteocalcin was most sensitive to the treatment of purmorphamine derivatives among genes we analyzed by RT-PCR. Purmorphamine derivatives differentially modulated the expression of early and late osteogenic markers; alkaline phosphatase and osteocalcin gene respectively. In addition, the expression of osteocalcin is also modulated differentially by purmorphamine derivatives over time. Although JNK activity is reported to be necessary for osteocalcin expression, its requirement varied among purmorphamine derivatives. Also the overall cytotoxic response to purmorphamine derivatives appeared slightly different.
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KEYWORD
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Sonic Hedgehog (SHH) signaling pathway, purmorphamine derivatives, osteogenesis, C2C12 premyoblasts, osteocalcin, alkaline phosphatase, JNK
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