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

Hironori Hojo, Fumiko Yano, Shinsuke Ohba, Kazuyo Igawa, Keiji Nakajima, Yuske Komiyama, Akinori Kan, Toshiyuki Ikeda, Takayuki Yonezawa, Je Tae Woo, Tsuyoshi Takato, Kozo Nakamura, Hiroshi Kawaguchi, Ung Il Chung

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)627-633
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume28
Issue number6
DOIs
Publication statusPublished - Nov 1 2010
Externally publishedYes

Keywords

  • BMP
  • Chondrocyte differentiation
  • Col2GFP-ATDC5
  • Osteoarthritis
  • Small compound

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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  • Cite this

    Hojo, H., Yano, F., Ohba, S., Igawa, K., Nakajima, K., Komiyama, Y., Kan, A., Ikeda, T., Yonezawa, T., Woo, J. T., Takato, T., Nakamura, K., Kawaguchi, H., & Chung, U. I. (2010). Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system. Journal of Bone and Mineral Metabolism, 28(6), 627-633. https://doi.org/10.1007/s00774-010-0179-y