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O ‐Phenanthroline as modulator of the hypoxic and catabolic response in cartilage tissue‐engineering models
Author(s) -
Georgi Nicole,
Landman Ellie B.M.,
Klein Travis J.,
Blitterswijk Clemens A.,
Karperien Marcel
Publication year - 2017
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1969
Subject(s) - chondrogenesis , chemistry , matrix metalloproteinase , cartilage , microbiology and biotechnology , explant culture , hypoxia (environmental) , in vitro , catabolism , anatomy , biochemistry , biology , oxygen , metabolism , organic chemistry
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 TNF α /IL‐1 β exposure in an explant model. Interestingly, O ‐phenanthroline significantly inhibited matrix degradation in a TNF α /IL‐1 β ‐dependent model of cartilage degeneration when compared to control and natural hypoxia (2.5% O 2 ). 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. Copyright © 2014 John Wiley & Sons, Ltd.