El Hajjaji Hafida, Marcelis Annette, Devogelaer Jean-Pierre, Manicourt Daniel-Henri
ICP Christian de Duve Institute of Cellular Pathology and the Department of Rheumatology, Saint-Luc University Hospital, Catholic University of Louvain, Avenue Mounier, 1200 Brussels, Belgium.
J Rheumatol. 2003 Nov;30(11):2444-51.
To assess the effects of celecoxib, a cyclooxygenase (COX-2) selective inhibitor, on the metabolism of hyaluronan (HA) and proteoglycans (PG) in human cartilage explants with midrange severity of osteoarthritis (OA). Results were compared with those of diclofenac, a non-selective COX inhibitor.
Cartilage specimens (OA grade 4-8 on Mankin's scale) were pulsed with 3H -glucosamine and chased in the absence or presence of 1-10 micro g/ml of celecoxib or diclofenac. After papain digestion, the labeled chondroitin sulfate and HA molecules were purified by anion-exchange chromatography.
Diclofenac did not affect the metabolic balance of PG and HA whereas, in a relatively dose-dependent manner, celecoxib increased the synthesis of HA and PG; celecoxib also reduced the net loss of labeled HA and PG molecules from cartilage explants.
In short term in vitro cultures, celecoxib has a favorable effect on the overall metabolism of PG and HA. It is therefore unlikely that this drug would have a detrimental effect on articular cartilage during longterm administration. Further, celecoxib might help counteract the depletion of HA seen in OA cartilage.
评估环氧化酶（COX-2）选择性抑制剂塞来昔布对中度骨关节炎（OA）严重程度的人软骨外植体中透明质酸（HA）和蛋白聚糖（PG）代谢的影响。将结果与非选择性COX抑制剂双氯芬酸的结果进行比较。
用3H-葡萄糖胺脉冲处理软骨标本（Mankin分级为4-8级OA），并在不存在或存在1-10μg/ml塞来昔布或双氯芬酸的情况下进行追踪。木瓜蛋白酶消化后，通过阴离子交换色谱法纯化标记的硫酸软骨素和HA分子。
双氯芬酸不影响PG和HA的代谢平衡，而塞来昔布以相对剂量依赖性方式增加HA和PG的合成；塞来昔布还减少了软骨外植体中标记的HA和PG分子的净损失。
在短期体外培养中，塞来昔布对PG和HA的整体代谢具有有利影响。因此，该药物在长期给药期间不太可能对关节软骨产生有害影响。此外，塞来昔布可能有助于抵消OA软骨中HA的消耗。
