Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Andrea R. Tan, Curtis D. VandenBerg, Mukundan Attur, Steven B. Abramson, Martin M Knight, J. Chloe Bulinski, Gerard A. Ateshian, James L Cook, Clark T. Hung

ABSTRACT

BACKGROUND: During osteoarthritis and following surgical procedures, the environment of the knee is rich in proinflammatory cytokines such as IL-1. Introduction of tissue-engineered cartilage constructs to a chemically harsh milieu may limit the functionality of the implanted tissue over long periods. A chemical preconditioning scheme (application of low doses of IL-1) was tested as a method to prepare developing engineered tissue to withstand exposure to a higher concentration of the cytokine, known to elicit proteolysis as well as rapid degeneration of cartilage. METHODS: Using an established juvenile bovine model system, engineered cartilage was preconditioned with low doses of IL-1α (0.1 ng/mL, 0.5 ng/mL, and 1.0 ng/mL) for 7 days before exposure to an insult dose (10 ng/mL). The time frame over which this protection is afforded was investigated by altering the amount of time between preconditioning and insult as well as the time following insult. To explore a potential mechanism for this protection, one set of constructs was preconditioned with CoCl2, a chemical inducer of hypoxia, before exposure to the IL-1α insult. Finally, we examined the translation of this preconditioning method to extend to clinically relevant adult, passaged chondrocytes from a preclinical canine model. RESULTS: Low doses of IL-1α (0.1 ng/mL and 0.5 ng/mL) protected against subsequent catabolic degradation by cytokine insult, preserving mechanical stiffness and biochemical composition. Regardless of amount of time between preconditioning scheme and insult, protection was afforded. In a similar manner, preconditioning with CoCl2 similarly allowed for mediation of catabolic damage by IL-1α. The effects of preconditioning on clinically relevant adult, passaged chondrocytes from a preclinical canine model followed the same trends with low-dose IL-1β offering variable protection against insult. CONCLUSIONS: Chemical preconditioning schemes have the ability to protect engineered cartilage constructs from IL-1-induced catabolic degradation, offering potential modalities for therapeutic treatments. More... »

PAGES

361

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-015-0876-y

DOI

http://dx.doi.org/10.1186/s13075-015-0876-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1018457428

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26667364


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