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Modulation of osteocalcin expression by purmorphamine derivatives

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Abstract

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 includingRunx2, Dlx2 andHes1. 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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References

  • Aikin RA, Ayers KL andTherond PP (2008) The role of kinases in the Hedgehog signalling pathway. EMBO Rep. 9: 330–336.

    Article  CAS  PubMed  Google Scholar 

  • Akiyama H, Chaboissier MC, Martin JF, Schedl A andde CB (2002) The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 16: 2813–2828.

    Article  CAS  PubMed  Google Scholar 

  • Beloti MM, Bellesini LS andRosa AL (2005) Purmorphamine enhances osteogenic activity of human osteoblasts derived from bone marrow mesenchymal cells. Cell Biol. Int. 29: 537–541.

    Article  CAS  PubMed  Google Scholar 

  • Briscoe J (2006) Agonizing hedgehog. Nat. Chem. Biol. 2: 10–11.

    Article  CAS  PubMed  Google Scholar 

  • Cancedda R, Castagnola P, Cancedda FD, Dozin B andQuarto R (2000) Developmental control of chondrogenesis and osteogenesis. Int. J. Dev. Biol. 44: 707–714.

    CAS  PubMed  Google Scholar 

  • Chari NS andMcDonnell TJ (2007) The sonic hedgehog signaling network in development and neoplasia. Adv. Anat. Pathol. 14: 344–352.

    Article  CAS  PubMed  Google Scholar 

  • Cohen MM Jr (2006) The new bone biology: pathologic, molecular, and clinical correlates. Am. J. Med. Genet. A 140: 2646–2706.

    PubMed  Google Scholar 

  • Eames BF, de la FL andHelms JA (2003) Molecular ontogeny of the skeleton. Birth Defects Res. C. Embryo. Today 69: 93–101.

    Article  CAS  PubMed  Google Scholar 

  • Guicheux J, Lemonnier J, Ghayor C, Suzuki A, Palmer G andCaverzasio J (2003) Activation of p38 mitogenactivated protein kinase and c-Jun-NH2- terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J. Bone Miner. Res. 18: 2060–2068.

    Article  CAS  PubMed  Google Scholar 

  • Hall BK andMiyake T (1992) The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anat. Embryol. (Berl) 186: 107–124.

    CAS  Google Scholar 

  • Jenkins D (2009) Hedgehog signalling: emerging evidence for non-canonical pathways. Cell Signal. 21: 1023–1034.

    Article  CAS  PubMed  Google Scholar 

  • Karsenty G andWagner EF (2002) Reaching a genetic and molecular understanding of skeletal development. Dev. Cell 2: 389–406.

    Article  CAS  PubMed  Google Scholar 

  • Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423: 332–336.

    Article  CAS  PubMed  Google Scholar 

  • Lee AJ, Hodges S andEastell R (2000) Measurement of osteocalcin. Ann. Clin. Biochem. 37 (Pt 4): 432–446.

    Article  PubMed  Google Scholar 

  • Lee SJ, Lee HK, Cho SY, Choi JK, Shin HK, Kwak EJ, Cho MR, Kim HR, Kim SR, Kim YM, Park KJ andChoi JK (2008) Identification of osteogenic purmorphamine derivatives. Mol. Cells 26: 380–386.

    CAS  PubMed  Google Scholar 

  • Mukai T, Otsuka F, Otani H, Yamashita M, Takasugi K, Inagaki K, Yamamura M andMakino H (2007) TNFalpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem. Biophys. Res. Commun. 356: 1004–1010.

    Article  CAS  PubMed  Google Scholar 

  • Shum L andNuckolls G (2002) The life cycle of chondrocytes in the developing skeleton. Arthritis Res. 4: 94–106.

    Article  CAS  PubMed  Google Scholar 

  • Sinha S andChen JK (2006) Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat. Chem. Biol. 2: 29–30.

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Ding S, Ding Q, Gray NS andSchultz PG (2002) A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells. J. Am. Chem. Soc. 124: 14520–14521.

    Article  CAS  PubMed  Google Scholar 

  • Wu X, Walker J, Zhang J, Ding S andSchultz PG (2004) Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway. Chem. Biol. 11: 1229–1238.

    Article  CAS  PubMed  Google Scholar 

  • Yu S, Franceschi RT, Luo M, Zhang X, Jiang D, Lai Y, Jiang Y, Zhang J andXiao G (2008) Parathyroid hormone increases activating transcription factor 4 expression and activity in osteoblasts: requirement for osteocalcin gene expression. Endocrinology 149: 1960–1968.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Dongguk University, 780-714, Gyeongju, Gyeongbuk, Korea

    Hye-Ryun Kim, So-Hee Jeong, Young-Sam Im & Joong-Kook Choi

  2. Drug Discovery Division, Korea Research Institute of Chemical Technology, 305-343, Daejeon, Korea

    Sung Yun Cho & Joong-Kwon Choi

  3. Department of Plastic Surgery, College of Medicine, Dongguk University, 780-714, Gyeongju, Gyeongbuk, Korea

    Hea Kyeong Shin

  4. Department of Orthopaedic Surgery, College of Medicine, Chungbuk National University, 361-763, Cheongju, Chungbuk, Korea

    Yong-Min Kim

  5. Gyeonggi Regional Research Center, Hankyong National University, 456-749, Ansung, Gyeonggi, Korea

    Jin-Ook Song

  6. College of Pharmacy, Kangwon National University, 200-701, Chuncheon, Korea

    Seong-Ho Jeon

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  1. Hye-Ryun Kim
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  2. So-Hee Jeong
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  3. Young-Sam Im
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  4. Sung Yun Cho
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  5. Joong-Kwon Choi
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  6. Hea Kyeong Shin
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  7. Yong-Min Kim
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  9. Seong-Ho Jeon
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  10. Joong-Kook Choi
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Correspondence to Joong-Kook Choi.

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Kim, HR., Jeong, SH., Im, YS. et al. Modulation of osteocalcin expression by purmorphamine derivatives. Genes & Genomics 31, 261–266 (2009). https://doi.org/10.1007/BF03191198

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  • DOI: https://doi.org/10.1007/BF03191198

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