Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University, Maastricht, The Netherlands.
Maastricht MultiModal Molecular Imaging Institute (M4i), Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, The Netherlands.
Cartilage. 2022 Jul-Sep;13(3):19476035221115541. doi: 10.1177/19476035221115541.
The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an osteoarthritis rat model.
Articular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E, prostaglandin F, prostaglandin D) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib , 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection.
Secretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human () explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an osteoarthritis knee rat model.
Our data demonstrated that celecoxib acts chondroprotective on cartilage and a single intra-articular bolus injection has a chondroprotective effect .
塞来昔布是一种非甾体抗炎药和选择性环氧化酶-2 抑制剂，用于减轻膝骨关节炎患者的疼痛和炎症，其潜在的软骨保护作用存在争议。本研究旨在探讨塞来昔布对（1）人关节软骨外植体和（2）骨关节炎大鼠模型的软骨保护作用。
16 例骨关节炎患者的关节软骨外植体用塞来昔布或载体培养 24 小时。通过 ELISA 测定培养基中前列腺素（前列腺素 E、前列腺素 F、前列腺素 D）和血栓素 B2（TXB2）的浓度，并采用无标记蛋白质组学方法测量蛋白质调节。对其中 7 例患者的软骨样本进行实时定量聚合酶链反应分析。为了研究塞来昔布的软骨保护作用，14 只大鼠在前交叉韧带切断和部分内侧半月板切除术（ACLT/pMMx 模型）诱导骨关节炎后，分别接受关节内注射塞来昔布或 0.9%氯化钠。注射后 12 周，采用组织病理学评分评估骨关节炎严重程度。
在人（）外植体培养中，塞来昔布处理后前列腺素、Nesh-SH3（ABI3BP）和骨粘连蛋白蛋白的分泌减少，而金属蛋白酶组织抑制剂 2（TIMP-2）显著增加。塞来昔布处理后，人软骨外植体中 a 型血小板反应蛋白 4 和 5（ADAMTS4/5）和基质金属蛋白酶 13（MMP13）的基因表达显著降低。骨关节炎大鼠模型中软骨退变明显减少。
我们的数据表明，塞来昔布对软骨具有软骨保护作用，单次关节内注射具有软骨保护作用。
