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Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system

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Abstract

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy’s induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.

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Acknowledgments

We thank Drs. K. Miyazono, T. Katagiri, J. Y. Choi, A. Hecht, and H. Sasaki for their kind distribution of experimental materials, as well as Astellas Pharma, Inc., for providing rhBMP2. H. Hojo was supported by Research Fellowships from the Japan Society for the Promotion of Science for Young Scientists. This work was supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (nos. 19390509 and 20390509).

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Authors and Affiliations

  1. Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hironori Hojo, Fumiko Yano, Shinsuke Ohba, Kazuyo Igawa, Keiji Nakajima, Yuske Komiyama & Ung-il Chung

  2. Department of Sensory and Motor System Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Fumiko Yano, Shinsuke Ohba, Kazuyo Igawa, Keiji Nakajima, Yuske Komiyama, Akinori Kan, Toshiyuki Ikeda, Tsuyoshi Takato, Kozo Nakamura & Hiroshi Kawaguchi

  3. Department of Nutriproteomics, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Takayuki Yonezawa & Je-Tae Woo

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  1. Hironori Hojo
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  2. Fumiko Yano
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  3. Shinsuke Ohba
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  9. Takayuki Yonezawa
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  11. Tsuyoshi Takato
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  12. Kozo Nakamura
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  14. Ung-il Chung
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Correspondence to Hironori Hojo or Ung-il Chung.

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Hojo, H., Yano, F., Ohba, S. et al. Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system. J Bone Miner Metab 28, 627–633 (2010). https://doi.org/10.1007/s00774-010-0179-y

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  • DOI: https://doi.org/10.1007/s00774-010-0179-y

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