O-Phenanthroline as modulator of the hypoxic and catabolic response in cartilage tissue-engineering models

Nicole Georgi, Ellie B.M. Landman, Travis J. Klein, Clemens A. van Blitterswijk, Marcel Karperien*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Hypoxia has been shown to be important for maintaining cartilage homeostasis as well as for inducing chondrogenic differentiation. Ensuring low oxygen levels during in vitro culture is difficult, therefore we assessed the chondro-inductive capabilities of the hypoxia-mimicking agent O-phenanthroline, which is also known as a non-specific matrix metalloproteinase (MMP) inhibitor. We found that O-phenanthroline reduced the expression of MMP3 and MMP13 mRNA levels during chondrogenic differentiation of human chondrocytes (hChs), as well as after TNFα/IL-1β exposure in an explant model. Interestingly, O-phenanthroline significantly inhibited matrix degradation in a TNFα/IL-1β-dependent model of cartilage degeneration when compared to control and natural hypoxia (2.5% O2). O-Phenanthroline had limited ability to improve the chondrogenic differentiation or matrix deposition in the chondrogenic pellet model. Additionally, O-phenanthroline alleviated MMP-induced cartilage degradation without affecting chondrogenesis in the explant culture. The data presented in this study indicate that the inhibitory effect of O-phenanthroline on MMP expression is dominant over the hypoxia-mimicking effect.

Original languageEnglish
Pages (from-to)724-732
Number of pages9
JournalJournal of tissue engineering and regenerative medicine
Volume11
Issue number3
Early online date21 Nov 2014
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • cartilage
  • chondrogenesis
  • degradation
  • differentiation
  • phenanthroline

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