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The effect of a cyclooxygenase 2 inhibitor on early degenerated human nucleus pulposus explants.

机译:环氧合酶2抑制剂对早期退化的人类髓核外植体的影响。

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Study Design?Preclinical in vitro culture of human degenerated nucleus pulposus (NP) tissue. Objective?Cyclooxygenase 2 inhibitors (e.g., celecoxib) inhibit prostaglandin E2 (PGE2) production, and they have been shown to upregulate regeneration of articular cartilage. In this study, we developed an explant culture system for use with human tissue and tested the potential of celecoxib. Methods?NP explants were cultured with or without 1 μM of celecoxib and were analyzed at days 0 and 7 for biochemical content (water, sulfated glycosaminoglycans, hydroxyproline, and DNA), gene expression (for disk matrix anabolic and catabolic markers), and PGE2 content. Results?Water and biochemical contents as well as gene expression remained close to native values after 1?week of culture. PGE2 levels were not increased in freshly harvested human NP tissue and thus were not reduced in treated tissues. Although no anabolic effects were observed at the dosage and culture duration used, no detrimental effects were observed and some specimens did respond by lowering PGE2. Conclusions?Human degenerated NP explants were successfully cultured in a close to in vivo environment for 1 week. Further research, especially dosage-response studies, is needed to understand the role of PGE2 in low back pain and the potential of celecoxib to treat painful disks.
机译:研究设计-人类退化髓核(NP)组织的临床前体外培养。目的?环氧合酶2抑制剂(例如塞来昔布(celecoxib))抑制前列腺素E2(PGE2)的产生,并已显示它们可上调关节软骨的再生。在这项研究中,我们开发了用于人体组织的外植体培养系统,并测试了塞来昔布的潜力。方法在有或没有1μM塞来昔布的情况下培养NP外植体,并在第0和第7天分析其生化含量(水,硫酸化糖胺聚糖,羟脯氨酸和DNA),基因表达(用于盘状基质合成代谢和分解代谢标记)和PGE2内容。结果培养1周后,水和生化含量以及基因表达保持接近天然值。在新鲜收获的人NP组织中PGE2水平没有增加,因此在治疗的组织中PGE2水平也没有降低。尽管在所用的剂量和培养时间中未观察到合成代谢作用,但未观察到有害作用,并且某些标本确实通过降低PGE2做出反应。结论:人类退化的NP外植体在接近体内的环境中成功培养了1周。需要进一步的研究,尤其是剂量反应研究,以了解PGE2在下背痛中的作用以及塞来昔布治疗疼痛性椎间盘的潜力。

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