The effect of thymosin β4 on articular cartilage chondrocyte matrix metalloproteinase expression

The effect of thymosin β4 on articular cartilage chondrocyte matrix metalloproteinase expression
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DOI:
10.1042/bst0300879
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发表时间:
2002-11-01
影响因子:
3.9
通讯作者:
Duance, VC
Duance, VC
中科院分区:
生物学3区
文献类型:
--
作者:
Blain, EJ;Mason, DJ;Duance, VC

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机械负荷在调节关节软骨软骨细胞的合成代谢和分解代谢活动中至关重要,对于基质保持其功能完整性至关重要。我们已经确定胸腺素β(4)是一种假定的机械调节基因,可能介导关节软骨中基质金属蛋白酶(MMPs)2和9的负荷增强合成和活化。本研究的目的是确认胸腺素β(4)的机械调节,并确定其对软骨软骨细胞MMP产生的影响。通过定量PCR分析的胸腺素β(4)mRNA表达显示,在加载10分钟的软骨中显著增加20倍,这在加载30分钟后仍然明显。用2和4 μ g. ml(-1)胸腺素β(4)肽作用4 h可显著增加MMP 9原的表达和活化。我们假设负荷诱导的胸腺素β(4)在调节关节软骨软骨细胞的细胞骨架组织以影响MMP表达中的功能作用。
Mechanical loading is paramount in regulating both the anabolic and catabolic activities of articular cartilage chondrocytes, essential for the matrix to retain its functional integrity. We have identified thymosin beta(4), as a putative mechanically regulated gene that may mediate load-enhanced synthesis and activation of matrix metalloproteinases (MMPs) 2 and 9 in articular cartilage. The objective of this study was to confirm the mechanical regulation of thymosin beta(4), and determine its effect on cartilage chondrocyte MMP production. Thymosin beta(4), mRNA expression, analysed by quantitative PCR, revealed a significant 20-fold increase in cartilage loaded for 10 min which was still evident after 30 min of loading. Treatment of primary chondrocytes with 2 and 4 mug . ml(-1) thymosin beta(4), peptide for 4 h significantly increased pro-MMP 9 expression and activation. We postulate a functional role for load-induced thymosin beta(4) in modulating the cytoskeletal organization of articular cartilage chondrocytes to affect MMP expression.