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首页> 外文期刊>Osteoarthritis and cartilage >Celecoxib exerts protective effects on extracellular matrix metabolism of mandibular condylar chondrocytes under excessive mechanical stress
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Celecoxib exerts protective effects on extracellular matrix metabolism of mandibular condylar chondrocytes under excessive mechanical stress

机译：Celecoxib在过度机械应力下对下颌髁突软骨细胞细胞外基质代谢产生保护作用

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摘要

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 0.5Hz, 10% elongation with celecoxib for 24h. 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-κB 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-κB 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.
机译：目的：过度的机械压力被认为是颞下颌关节骨关节炎（TMJ-OA）的主要原因。高级环状拉伸菌株（CTS）上调节软骨细胞的促炎细胞因子和基质金属蛋白酶（MMP），而选择性环氧酶（COX）-2抑制已被证明是有益于细胞因子诱导的软骨损伤。然而，选择性Cox-2抑制剂对机械刺激的软骨细胞的影响仍不清楚。该研究评估了Celecoxib，一种选择性COX-2抑制剂对CTS下颌骨髁突软骨细胞细胞外基质（ECM）代谢的影响。方法：将猪下颌软骨细胞进行0.5Hz的CTS，用塞克昔布伸长10％伸长24小时。通过实时PCR检查Cox-2，MMP，聚合物酶（Adamts），II型胶原蛋白和蛋白酶的基因表达。此外，使用酶免疫测定试剂盒测定前列腺素E2（PGE2）浓度。通过蛋白质印迹测量MMP和转录因子NF-κB的水平，而MMP活性由酪蛋白酶谱系测定。结果：Celecoxib的存在归一化PGE2的释放，并降低了CTS诱导的COX-2，MMP-1，MMP-3，MMP-9和ADAMTS-5基因表达，同时回收了下调的II型胶原和蛋白基因表达。同时，Celecoxib表现出NF-κB的抑制和MMP生产和活性的抑制。结论：Celecoxib通过降低降解和恢复ECM的合成，对CTS刺激的颌骨髁突软骨细胞的保护作用。

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  • 来源
    《Osteoarthritis and cartilage》 |2014年第6期|共7页
  • 作者

    SuS.-C.; TanimotoK.; TanneY.; KunimatsuR.; HiroseN.; MitsuyoshiT.; OkamotoY.; TanneK.;

  • 作者单位

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

    Department of Orthodontics Division of Applied Biosciences Hiroshima University Graduate School;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 骨科学（运动系疾病、矫形外科学）;
  • 关键词

    Celecoxib; Chondrocyte; Extracellular matrix; Matrix metalloproteinases; Mechanical stress;

    机译：Celecoxib;软骨细胞;细胞外基质;基质金属蛋白酶;机械应力;

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