| 12954240 |
Chowdhury TT, Bader DL, Lee DA: Dynamic compression counteracts IL-1 beta-induced release of nitric oxide and PGE2 by superficial zone chondrocytes cultured in agarose constructs. Osteoarthritis Cartilage. 2003 Sep;11(9):688-96.
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. DESIGN: 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. CONCLUSION: 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. |
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