Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids.

Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids.
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抗炎药治疗骨关节炎的研究:环氧酶-2抑制剂和类固醇。

DOI:
10.1155/2015/595273
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发表时间:
2015
影响因子:
--
通讯作者:
Hasty KA
Hasty KA
中科院分区:
生物学3区
文献类型:
--
作者:
Cho H;Walker A;Williams J;Hasty KA

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骨关节炎(OA)是一种以软骨退化为特征的疾病,通常用类固醇、非甾体抗炎药(NSAID)和环氧合酶-2(考克斯-2)选择性NSAID治疗。由于它们抑制炎症级联反应,药物影响基质金属蛋白酶(MMP)和炎性细胞因子的平衡,导致细胞外基质(ECM)的保存。为了比较这些处理对软骨细胞代谢的影响,将TNF-α与培养的软骨细胞一起孵育,以模拟促炎环境,增加MMP-1和前列腺素E2(PGE 2)的产生。然后用类固醇(泼尼松)、非特异性考克斯抑制剂NSAID(吡罗昔康)或考克斯-2选择性NSAID(塞来昔布)处理软骨细胞。泼尼松和塞来昔布均降低MMP-1和PGE-2的产生,而非特异性吡罗昔康仅降低后者。泼尼松和塞来昔布均降低MMP-1基因表达,增加聚集蛋白聚糖的表达。塞来昔布组II型胶原基因表达也增加。非特异性吡罗昔康未显示这些作用。使用创伤后OA(PTOA)小鼠模型研究塞来昔布的体内疗效。在体内,塞来昔布增加聚集蛋白聚糖的合成并抑制MMP-1。总之,这项研究表明,塞来昔布和类固醇发挥类似的作用,MMP-1和PGE 2的生产在体外和塞来昔布可能表现出有益的影响,在体内的合成代谢。
Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.
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