The influence of oxygen tension on the induction of nitric oxide and prostaglandin E2 by mechanical stress in articular cartilage.
OBJECTIVE
Articular cartilage is an avascular tissue that exists at low oxygen tension. Oxygen tension can influence the production of the pro-inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE(2)) in cartilage, which are increased in osteoarthritis (OA). The synthesis of these molecules can be stimulated by mechanical stress, which is an important risk factor for OA. The objective of this study was to determine the influence of oxygen tension on the induction of NO and PGE(2) production in articular cartilage in response to mechanical stress.


METHODS
Intermittent mechanical compression (0.05MPa, 0.5Hz for 24h) was applied to full thickness skeletally mature porcine articular cartilage explants at either 20%, 5%, or 1% O(2). NO, PGE(2) and peroxynitrite formation were measured, and the effect of the selective nitric oxide synthase 2 inhibitor 1400W was tested.


RESULTS
Incubating articular cartilage at 5% O(2) significantly increased (P<0.001) baseline NO production, as compared with 1% or 20% O(2). Peroxynitrite formation was lower at reduced oxygen tension. Mechanical compression significantly increased (P<0.001) NO production at 20% O(2) but not at 5% or 1% O(2), and significantly increased (P<0.001) PGE(2) production at 20% O(2) (50 fold) and 5% O(2) (4 fold) but not at 1% O(2). 1400W blocked mechanically induced NO production and further increased PGE(2) production at 5% O(2) (P<0.05).


CONCLUSIONS
Oxygen tension influences the endogenous production of NO and PGE(2) in cartilage and can have a significant effect on the induction of these inflammatory mediators in response to mechanical compression.
Department of Surgery, Division of Orthopaedic Surgery, Box 3093, Duke University Medical Center, NC 27710, USA. bfer@duke.edu
Beverley
B
Fermor
J Brice
JB
Weinberg
David S
DS
Pisetsky
Farshid
F
Guilak
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010100:Oxygen / Q000097:blood*; D013314:Stress, Mechanical; D013552:Swine; D046509:Tissue Culture Techniques; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D018836:Inflammation Mediators; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D015232:Dinoprostone; D010100:Oxygen