氨基葡萄糖和硫酸软骨素调节关节软骨外植体中一氧化氮和前列腺素E2的基因表达及合成。

Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants.

作者信息

Chan P S, Caron J P, Rosa G J M, Orth M W

机构信息

Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.

出版信息

Osteoarthritis Cartilage. 2005 May;13(5):387-94. doi: 10.1016/j.joca.2005.01.003.

DOI:10.1016/j.joca.2005.01.003

PMID:15882562

Abstract

OBJECTIVE

Glucosamine (GLN) and chondroitin sulfate (CS) are widely used to alleviate symptoms of osteoarthritis (OA). However, the mechanism(s) of action of these nutraceuticals remains unresolved. In the present study, we determined the effect of physiologically relevant concentrations of GLN and CS on gene expression and synthesis of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in cytokine-stimulated articular cartilage explants.

METHODS

Using bovine articular cartilage explants in culture stimulated with IL-1, the effects of physiologically relevant concentrations of GLN and CS on gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGEs1) were assessed with quantitative real-time polymerase chain reaction (Q-RT-PCR). The production of NO and PGE(2) was also quantified.

RESULTS

CS and the GLN and CS combination at concentrations attainable in the blood down-regulated IL-1 induced mRNA expression of iNOS at 24 and 48 h post-culture. Up-regulated iNOS expression at 24h by IL-1 was also suppressed by GLN. GLN and CS transiently repressed the cytokine-stimulated mPGEs1 transcript. Synthesis of NO was reduced with CS alone and the combination after 24h of culture. Repression of COX-2 transcripts by GLN and CS was accompanied by concomitant reduction in PGE(2).

CONCLUSION

Our results indicate that physiologically relevant concentrations of GLN and CS can regulate gene expression and synthesis of NO and PGE(2), providing a plausible explanation for their purported anti-inflammatory properties.

摘要

目的

氨基葡萄糖（GLN）和硫酸软骨素（CS）被广泛用于缓解骨关节炎（OA）症状。然而，这些营养保健品的作用机制仍未明确。在本研究中，我们测定了生理相关浓度的GLN和CS对细胞因子刺激的关节软骨外植体中一氧化氮（NO）和前列腺素E2（PGE2）基因表达及合成的影响。

方法

使用白细胞介素-1刺激培养的牛关节软骨外植体，通过定量实时聚合酶链反应（Q-RT-PCR）评估生理相关浓度的GLN和CS对诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS）、环氧化酶-2（COX-2）和微粒体前列腺素E合酶-1（mPGEs1）基因表达的影响。同时对NO和PGE2的产生进行定量分析。

结果

CS以及血液中可达到浓度的GLN与CS组合在培养24小时和48小时后下调了白细胞介素-1诱导的iNOS mRNA表达。GLN也抑制了白细胞介素-1在24小时时上调的iNOS表达。GLN和CS短暂抑制了细胞因子刺激的mPGEs1转录本。单独使用CS以及培养24小时后的组合均降低了NO的合成。GLN和CS对COX-2转录本的抑制伴随着PGE2的相应减少。