TY - JOUR
T1 - Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants
AU - Hardy, Medora M.
AU - Seibert, Karen
AU - Manning, Pamela T.
AU - Currie, Mark G.
AU - Woerner, B. Mark
AU - Edwards, Dorothy
AU - Koki, Alane
AU - Tripp, Catherine S.
PY - 2002
Y1 - 2002
N2 - Objective. To examine cyclooxygenase-2 (COX-2) enzyme expression, its regulation by interleukin-1β (IL-1β), and the role of prostaglandin E2 (PGE2) in proteoglycan degradation in human osteoarthritic (OA) cartilage. Methods. Samples of human OA articular cartilage, meniscus, synovial membrane, and osteophytic fibrocartilage were obtained at knee arthroplasty and cultured ex vivo with or without IL-1β and COX inhibitors. COX expression was evaluated by immunohistochemistry and Western blot analysis. The enzymatic activity of COX was measured by conversion of arachidonic acid to PGE2. Cartilage degradation was evaluated by measuring the accumulation of sulfated glycosaminoglycans in the medium. Results. IL-1β induced robust expression of COX-2 and PGE2 in OA meniscus, synovial membrane, and osteophytic fibrocartilage explants, whereas low levels were produced in OA articular cartilage. IL-1β also induced cartilage proteoglycan degradation in OA synovial membrane-cartilage cocultures. Increased proteoglycan degradation corresponded to the induction of COX-2 protein expression in, and PGE2 production from, the synovial membrane. Dexamethasone, neutralizing IL-1β antibody, or the selective COX-2 inhibitor, SC-236, attenuated both the IL-1β-induced PGE2 production and cartilage proteoglycan degradation in these cocultures. The addition of PGE2 reversed the inhibition of proteoglycan degradation caused by SC-236. Conclusion. IL-1β-induced production of COX-2 protein and PGE2 was low in OA articular cartilage compared with that in the other OA tissues examined. IL-1β-mediated degradation of cartilage proteoglycans in OA synovial membrane-cartilage cocultures was blocked by the selective COX-2 inhibitor, SC-236, and the effect of SC-236 was reversed by the addition of exogenous PGE2. Our data suggest that induction of synovial COX-2-produced PGE2 is one mechanism by which IL-1β modulates cartilage proteoglycan degradation in OA.
AB - Objective. To examine cyclooxygenase-2 (COX-2) enzyme expression, its regulation by interleukin-1β (IL-1β), and the role of prostaglandin E2 (PGE2) in proteoglycan degradation in human osteoarthritic (OA) cartilage. Methods. Samples of human OA articular cartilage, meniscus, synovial membrane, and osteophytic fibrocartilage were obtained at knee arthroplasty and cultured ex vivo with or without IL-1β and COX inhibitors. COX expression was evaluated by immunohistochemistry and Western blot analysis. The enzymatic activity of COX was measured by conversion of arachidonic acid to PGE2. Cartilage degradation was evaluated by measuring the accumulation of sulfated glycosaminoglycans in the medium. Results. IL-1β induced robust expression of COX-2 and PGE2 in OA meniscus, synovial membrane, and osteophytic fibrocartilage explants, whereas low levels were produced in OA articular cartilage. IL-1β also induced cartilage proteoglycan degradation in OA synovial membrane-cartilage cocultures. Increased proteoglycan degradation corresponded to the induction of COX-2 protein expression in, and PGE2 production from, the synovial membrane. Dexamethasone, neutralizing IL-1β antibody, or the selective COX-2 inhibitor, SC-236, attenuated both the IL-1β-induced PGE2 production and cartilage proteoglycan degradation in these cocultures. The addition of PGE2 reversed the inhibition of proteoglycan degradation caused by SC-236. Conclusion. IL-1β-induced production of COX-2 protein and PGE2 was low in OA articular cartilage compared with that in the other OA tissues examined. IL-1β-mediated degradation of cartilage proteoglycans in OA synovial membrane-cartilage cocultures was blocked by the selective COX-2 inhibitor, SC-236, and the effect of SC-236 was reversed by the addition of exogenous PGE2. Our data suggest that induction of synovial COX-2-produced PGE2 is one mechanism by which IL-1β modulates cartilage proteoglycan degradation in OA.
UR - http://www.scopus.com/inward/record.url?scp=0036064137&partnerID=8YFLogxK
U2 - 10.1002/art.10356
DO - 10.1002/art.10356
M3 - Article
C2 - 12124863
AN - SCOPUS:0036064137
SN - 0004-3591
VL - 46
SP - 1789
EP - 1803
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 7
ER -