Localization and characterization of the response of chondrocytes to mechanical load using in-situ hybridization

MacFarland, A.K.; Ewen, S. W. B.; Hoyland, JA; Aigner, Thomas; Keenan, George L.; Cordiner, D.; Aspden, Richard M.

doi:10.1016/0945-053x(94)90089-2

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“…There is considerable evidence that the cytokine interleukin-1 (IL-1) plays an important role in OA, being up-regulated in OA synovium and cartilage [ 8 , 9 ]. IL-1β expression in articular cartilage is also regulated by mechanical factors [ 10 ]. It induces a catabolic cascade involving the cyclooxygenase (COX) enzymes; two isoforms of which, COX-1 and COX-2, catalyse the conversion of arachidonic acid to prostaglandins (PG), the major pro-inflammatory product being prostaglandin E 2 (PGE 2 ) [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase inhibition lowers prostaglandin E2 release from articular cartilage and reduces apoptosis but not proteoglycan degradation following an impact load in vitro

Jeffrey

Aspden

2007

Arthritis Res Ther

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This study investigated the release of prostaglandin E 2 (PGE 2 ) from cartilage following an impact load in vitro and the possible chondroprotective effect of cyclooxygenase-2 (COX-2) inhibition using non-steroidal anti-inflammatory drugs (NSAIDs).Explants of human articular cartilage were subjected to a single impact load in a drop tower, and then cultured for 6 days in the presence of either a selective COX-2 inhibitor (celecoxib; 0.01, 0.1, 1.0 and 10 μM) or a non-selective COX inhibitor (indomethacin; 0.1 and 10 μM). The concentrations of PGE 2 and glycosaminoglycans (GAGs), a measure of cartilage breakdown, were measured in the explant culture medium at 3 and 6 days post-impact. Apoptotic cell death was measured in frozen explant sections by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method. PGE 2 levels were increased by more than 20-fold in the medium of explants at both 3 (p = 0.012) and 6 days (p = 0.004) following impact, compared with unloaded controls. In the presence of celecoxib and indomethacin, the PGE 2 levels were reduced in a dose-related manner. These inhibitors, however, had no effect in reducing the impact-induced release of GAGs from the cartilage matrix. Addition of celecoxib and indomethacin significantly reduced the number of traumainduced apoptotic chondrocytes in cartilage explant sections.In this study, a marked increase in PGE 2 was measured in the medium following an impact load on articular cartilage, which was abolished by the selective COX-2 inhibitor, celecoxib, and non-selective indomethacin. These inhibitors reduced chondrocyte apoptosis but no change was observed in the release of GAGs from the explants, suggesting that the COX/ PGE 2 pathway is not directly responsible for cartilage breakdown following traumatic injury. Our in vitro study demonstrates that it is unlikely that COX-2 inhibition alone would slow down or prevent the development of secondary osteoarthritis.

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Section: Introductionmentioning

confidence: 99%