title: Dynamic compression counteracts IL-1 beta-induced release of nitric oxide and PGE2 by superficial zone chondrocytes cultured in agarose constructs.
abstract: OBJECTIVE
  To examine the effect of IL-1 beta-induced *NO and PGE(2)release by stimulated superficial and deep chondrocyte/agarose constructs subjected to mechanical compression.
  
  
  METHODS
  Chondrocyte sub-populations were seeded separately in agarose constructs and cultured unstrained, within a 24-well tissue culture plate, for 48 h in medium supplemented with IL-1 beta and/or L-N-(1-iminoethyl)-ornithine (L-NIO). In a separate experiment, superficial and deep cell containing constructs were subjected to 15% dynamic compressive strain at 1 Hz, for 48 h, in the presence or absence of IL-1 beta and/or L-NIO. Nitrite was measured using the Griess assay, PGE(2)release was determined using an EIA kit and [3H]-thymidine and 35SO(4)incorporation were assessed by TCA and alcian blue precipitation, respectively.
  
  
  RESULTS
  The current data reveal that IL-1 beta significantly enhanced *NO and PGE(2)release for superficial chondrocytes, an effect reversed with L-NIO. *NO and PGE(2)levels did not significantly change by deep cells in the presence of IL-1 beta and/or L-NIO. For both cell sub-populations, IL-1 beta inhibited cell proliferation whereas proteoglycan synthesis was not affected. Dynamic compression inhibited the release of *NO and PGE(2)in the presence and absence of IL-1 beta, for cells from both sub-populations. L-NIO reduced *NO and enhanced PGE(2)release for superficial zone chondrocytes, an effect not observed for deep cells in response to dynamic compression. The magnitude of stimulation of [3H]-thymidine incorporation was similar for both cell sub-populations and was not influenced by L-NIO, indicating an z.rad;NO-independent pathway. The dynamic compression-induced stimulation of 35SO(4)incorporation was enhanced with L-NIO for IL-1 beta-stimulated deep cells, indicating an *NO-dependent pathway.
  
  
  CONCLUSIONS
  The present findings suggest that dynamic compression inhibits *NO and PGE(2)release in IL-1 beta-stimulated superficial cells via distinct pathways, a significant finding that may contribute to the development of intervention strategies for the treatment of inflammatory joint disorders.
authors.affiliation: Medical Engineering Division and IRC in Biomedical Materials, Department of Engineering, Queen Mary, University of London, Mile End Road, London, UK. t.t.chowdhury@qmul.ac.uk
authors.forename: T T
authors.initials: TT
authors.lastname: Chowdhury
authors.forename: D L
authors.initials: DL
authors.lastname: Bader
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D012685:Sepharose; D013314:Stress, Mechanical
chemical_list: D007375:Interleukin-1; D009569:Nitric Oxide; D012685:Sepharose; D015232:Dinoprostone