title: Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult.
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.
authors.affiliation: Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Avenue, New York, NY, USA. art2122@columbia.edu.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Tan
authors.affiliation: Department of Orthopedic Surgery, St. Luke's-Roosevelt Hospital Center, 1000 10th Avenue, New York, NY, USA. curtisvandenberg@gmail.com.
authors.forename: Curtis D
authors.initials: CD
authors.lastname: VandenBerg
authors.affiliation: New York University Hospital for Joint Disease, 301 E. 17th Street, New York, NY, USA. mukundan.attur@nyumc.org.
authors.forename: Mukundan
authors.initials: M
authors.lastname: Attur
authors.affiliation: New York University Hospital for Joint Disease, 301 E. 17th Street, New York, NY, USA. stevenb.abramson@nyumc.org.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
authors.affiliation: Institute of Bioengineering and School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, London, UK. m.m.knight@qmul.ac.uk.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Knight
authors.affiliation: Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY, USA. jcb4@columbia.edu.
authors.forename: J Chloe
authors.initials: JC
authors.lastname: Bulinski
authors.affiliation: Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Avenue, New York, NY, USA. ga29@columbia.edu.|Department of Mechanical Engineering, Columbia University, 500 W. 120th Street, New York, NY, USA. ga29@columbia.edu.
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Ateshian
authors.affiliation: Comparative Orthopaedic Laboratory, University of Missouri, 1100 Virginia Avenue, Columbia, MO, USA. cookjl@health.missouri.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Cook
authors.affiliation: Department of Biomedical Engineering, Columbia University, 1210 Amsterdam Avenue, New York, NY, USA. cth6@columbia.edu.
authors.forename: Clark T
authors.initials: CT
authors.lastname: Hung
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000473:pathology*; D016207:Cytokines / Q000276:immunology / Q000633:toxicity*; D004195:Disease Models, Animal; D004285:Dogs; D053582:Interleukin-1alpha / Q000276:immunology / Q000633:toxicity*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D016207:Cytokines; D053582:Interleukin-1alpha