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In vitro and in vivo osteogenic activity of licochalcone A

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Abstract

We investigated the in vitro and in vivo osteogenic activity of licochalcone A. At low concentrations, licochalcone A stimulated the differentiation of mouse pre-osteoblastic MC3T3-E1 subclone 4 (MC4) cells and enhanced the bone morphogenetic protein (BMP)-2-induced stimulation of mouse bi-potential mesenchymal precursor C2C12 cells to commit to the osteoblast differentiation pathway. This osteogenic activity of licochalcone A was accompanied by the activation of extracellular-signal regulated kinase (ERK). The involvement of ERK was confirmed in a pharmacologic inhibition study. Additionally, noggin (a BMP antagonist) inhibited the osteogenic activity of licochalcone A in C2C12 cells. Licochalcone A also enhanced the BMP-2-stimulated expression of various BMP mRNAs. This suggested that the osteogenic action of licochalcone A in C2C12 cells could be dependent on BMP signaling and/or expression. We then tested the in vivo osteogenic activity of licochalcone A in two independent animal models. Licochalcone A accelerated the rate of skeletal development in zebrafish and enhanced woven bone formation over the periosteum of mouse calvarial bones. In summary, licochalcone A induced osteoblast differentiation with ERK activation in both MC4 and C2C12 cells and it exhibited in vivo osteogenic activity in zebrafish skeletal development and mouse calvarial bone formation. The dual action of licochalcone A in stimulating bone formation and inhibiting bone resorption, as described in a previous study, might be beneficial in treating bone-related disorders.

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Acknowledgments

CHK was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1020090). This study was supported by a grant from the National R&D program of the Korea Ministry of Education, Science, and Technology, Republic of Korea (Chemical Genomics Research, 20100002073).

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Authors and Affiliations

  1. Laboratory of Chemical Genomics, Pharmacology Research Center, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea

    Soon Nam Kim, Su Jung Bae, Yong Ki Min & Seong Hwan Kim

  2. Department of Anatomy, School of Medicine, Wonkwang University, Chonbuk, Iksan, 570-749, Republic of Korea

    Han Bok Kwak

  3. Department of Biology and GRAST, Chungnam National University, Daejeon, 305-764, Republic of Korea

    Seung-Hyun Jung & Cheol-Hee Kim

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  1. Soon Nam Kim
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  2. Su Jung Bae
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Correspondence to Cheol-Hee Kim or Seong Hwan Kim.

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S. H. Kim and C. H. Kim are corresponding authors. S. N. Kim and S. J. Bae contributed equally to this study.

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Kim, S.N., Bae, S.J., Kwak, H.B. et al. In vitro and in vivo osteogenic activity of licochalcone A. Amino Acids 42, 1455–1465 (2012). https://doi.org/10.1007/s00726-011-0901-7

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