Background class='Para'>Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory cond'/> Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β
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首页> 外文期刊>Journal of orthopaedics and traumatology: official journal of the Italian Society of Orthopaedics and Traumatology >Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β
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Pravastatin suppresses matrix metalloproteinase expression and activity in human articular chondrocytes stimulated by interleukin-1β

机译：普伐他汀抑制白介素-1β刺激的人关节软骨细胞中基质金属蛋白酶的表达和活性

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class="Heading">Background class="Para">Matrix metalloproteinases are catabolic enzymes that play a key role in the articular cartilage degeneration evident in degenerative and inflammatory conditions of articular cartilage. The aim of this study is to assess the ability of pravastatin to modify matrix metalloproteinase (MMP) messenger RNA (mRNA) expression and enzyme activity in a culture of normal human chondrocytes stimulated by interleukin-1β. class="Heading">Materials and methods class="Para">Normal human chondrocytes were stimulated with interleukin (IL)-1β for 6?h to induce MMP expression, simulating a catabolic state, and then treated with pravastatin (1, 5 and 10?μM) for a further 18?h before cell lysates and supernatants were harvested. Cells stimulated with IL-1β but not treated with pravastatin served as controls. Real-time polymerase chain reaction (PCR) was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Statistical analysis was performed using analysis of variance (ANOVA). class="Heading">Results class="Para">MMP-3 and MMP-9 mRNA expression was reduced at all concentrations tested with statistically significant trends in reduction (p?=?0.002 and 0.001, respectively). Analysis of culture supernatants revealed that pravastatin treatment led to a reduction in total MMP activity but not to a statistically significant degree (p?=?0.07). class="Heading">Conclusions class="Para">Treatment with pravastatin of stimulated human chondrocytes leads to significant down-regulation of selected MMP genes and a non-significant reduction in MMP enzyme activity. Our results provide further evidence that statins may have a role to play in future treatment of disease affecting articular chondrocytes.
机译：class =“ Heading”>背景 class =“ Para”>基质金属蛋白酶是分解代谢酶，在关节软骨的退行性和炎症性疾病中，在关节软骨变性中起关键作用。这项研究的目的是评估普伐他汀在白细胞介素-1β刺激的正常人软骨细胞培养物中修饰基质金属蛋白酶（MMP）信使RNA（mRNA）表达和酶活性的能力。 class =“ Heading“>材料和方法 class =” Para“>用白介素（IL）-1β刺激正常人软骨细胞6？h，以诱导MMP表达，模拟分解代谢状态，然后用普伐他汀处理（在收集细胞裂解物和上清液之前，先将其分别置于1、5和10？μM），18？h的时间。用IL-1β刺激但未用普伐他汀处理的细胞作为对照。实时聚合酶链反应（PCR）用于评估MMP-3和MMP-9 mRNA的表达。使用荧光MMP特异性底物评估MMP酶活性。使用方差分析（ANOVA）进行统计分析。 class =“ Heading”>结果 class =“ Para”> MMP-3和MMP-9 mRNA的表达都降低了浓度的降低具有统计学上的显着趋势（ p ？=？0.002和<0.001）。对培养上清液的分析表明，普伐他汀治疗可导致总MMP活性降低，但未达到统计学上的显着水平（ p ？=？0.07）。 类普伐他汀治疗受刺激的人软骨细胞会导致所选MMP基因的显着下调和MMP酶活性的非显着降低。我们的结果提供了进一步的证据，证明他汀类药物可能在将来影响关节软骨细胞疾病的治疗中发挥作用。

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