Celecoxib exerts protective effects on extracellular matrix metabolism of mandibular condylar chondrocytes under excessive mechanical stress
Celecoxib exerts protective effects on extracellular matrix metabolism of mandibular condylar chondrocytes under excessive mechanical stress
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DOI：
10.1016/j.joca.2014.03.011
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发表时间：
2014-06-01
影响因子：
7
通讯作者：
Tanne, K.
中科院分区：
文献类型：
--
作者：
Su, S. -C.;Tanimoto, K.;Tanne, K.
目的：过度的机械应力被认为是颞下颌关节骨性关节炎（TMJ-OA）的主要原因。高强度循环拉伸应变（CTS）上调软骨细胞中的促炎细胞因子和基质金属蛋白酶（MMPs），而选择性环氧合酶(COX)-2抑制已被证明有利于细胞因子诱导的软骨损伤。然而，选择性COX-2抑制剂对机械刺激软骨细胞的影响尚不清楚。本研究评估了选择性COX-2抑制剂塞来昔布对CTS下下颌髁突软骨细胞细胞外基质（ECM）代谢的影响。方法：用塞来昔布对猪下颌软骨细胞施加0.5 Hz、10%延伸率的CTS作用24 h，采用实时荧光定量PCR检测COX-2、MMPs、聚集酶（ADAMTS）、II型胶原和聚集蛋白的基因表达。同时，采用酶免疫分析法检测前列腺素E2 （PGE2）浓度。western blot法测定MMP和转录因子nf - κ B水平，酪蛋白酶谱法测定MMP活性。结果：塞来昔布的存在使PGE2的释放正常化，cts诱导的COX-2、MMP-1、MMP-3、MMP-9和ADAMTS-5基因表达降低，而下调的II型胶原和聚集蛋白基因表达恢复。同时，塞来昔布显示抑制NF-kappa B和抑制MMP的产生和活性。结论：塞来昔布对CTS刺激下的下颌髁突软骨细胞具有保护作用，其机制是抑制ECM的降解，恢复ECM的合成。(C) 2014年由Elsevier Ltd代表国际骨关节炎研究学会出版。
Objective: Excessive mechanical stress is considered a major cause of temporomandibular joint osteoarthritis (TMJ-OA). High magnitude cyclic tensile strain (CTS) up-regulates pro-inflammatory cytokines and matrix metalloproteinases (MMPs) in chondrocytes, while selective cyclooxygenase (COX)-2 inhibition has been shown to be beneficial to cytokine-induced cartilage damage. However, the effect of selective COX-2 inhibitors on mechanically stimulated chondrocytes remains unclear. This study evaluated the effect of celecoxib, a selective COX-2 inhibitor, on extracellular matrix (ECM) metabolism of mandibular condylar chondrocytes under CTS.Methods: Porcine mandibular chondrocytes were subjected to CTS of 0.5 Hz, 10% elongation with celecoxib for 24 h. The gene expressions of COX-2, MMPs, aggrecanase (ADAMTS), type II collagen and aggrecan were examined by real-time PCR. Also, prostaglandin E2 (PGE2) concentrations were determined using enzyme immunoassay kit. The levels of MMP and transcription factor NF-kappa B were measured by western blot while MMP activity was determined by casein zymography.Results: The presence of celecoxib normalized the release of PGE2 and diminished the CTS-induced COX-2, MMP-1, MMP-3, MMP-9 and ADAMTS-5 gene expressions while recovered the downregulated type II collagen and aggrecan gene expressions. Concurrently, celecoxib showed inhibition of NF-kappa B and suppression of MMP production and activity.Conclusions: Celecoxib exerts protective effects on mandibular condylar chondrocytes under CTS stimulation by diminishing degradation and restoring synthesis of ECM. (C) 2014 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.