Synthetic triterpenoids, CDDO-Imidazolide and CDDO-Ethyl amide, induce chondrogenesis

N. Suh, S. Paul, H. J. Lee, T. Yoon, N. Shah, A. I. Son, A Hari Reddi, D. Medici, M. B. Sporn

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Novel methods for inducing chondrogenesis are critical for cartilage tissue engineering and regeneration. Here we show that the synthetic oleanane triterpenoids, CDDO-Imidazolide (CDDO-Im) and CDDO-Ethyl amide (CDDO-EA), at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of newborn mouse calvaria. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Furthermore, real-time polymerase chain reaction (PCR) analysis using mRNA from calvaria after 7-day treatment with CDDO-Im and CDDO-EA showed up-regulation of the chondrocyte markers SOX9 and type II collagen (alpha1). In addition, TGF-β; BMPs 2 and 4; Smads 3, 4, 6, and 7; and TIMPs-1 and -2 were increased. In contrast, MMP-9 was strongly down-regulated. Treatment of human bone marrow-derived mesenchymal stem cells with CDDO-Im and CDDO-EA (100 nM) induced expression of SOX9, collagen IIα1, and aggrecan, as well as BMP-2 and phospho-Smad5, confirming that the above triterpenoids induce chondrogenic differentiation. This is the first report of the use of these drugs for induction of chondrogenesis.

Original languageEnglish (US)
Pages (from-to)446-450
Number of pages5
JournalOsteoarthritis and Cartilage
Volume20
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Calvarial organ cultures
  • Chondrogenesis
  • Stem cells
  • Synthetic oleanane triterpenoids
  • Triterpenoids

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

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    Suh, N., Paul, S., Lee, H. J., Yoon, T., Shah, N., Son, A. I., Reddi, A. H., Medici, D., & Sporn, M. B. (2012). Synthetic triterpenoids, CDDO-Imidazolide and CDDO-Ethyl amide, induce chondrogenesis. Osteoarthritis and Cartilage, 20(5), 446-450. https://doi.org/10.1016/j.joca.2012.01.018