The transcription factor SOX9 (Sry-type high-mobility-group box 9) is expressed in all chondrocytes and is essential for the expression of aggrecan, which during biosynthesis is substituted with more than 10 times its weight of CS (chondroitin sulfate) and is secreted by chondrocytes to form the characteristic GAG (glycosaminoglycan)-rich ECM (extracellular matrix) of cartilage. SOX9 expression rapidly falls during monolayer culture of isolated chondrocytes and this turns off aggrecan and associated CS synthesis. We therefore investigated whether SOX9 transduction of cultured human articular chondrocytes had any effect on the gene expression of the glycosyltransferases and sulfotransferases necessary for GAG biosynthesis. Retroviral SOX9 transduction of passaged chondrocytes increased the endogenous rate of GAG synthesis and the total capacity for GAG synthesis assessed in monolayer culture with beta-xyloside. Both the endogenous rate and the total capacity of GAG biosynthesis were increased further in chondrogenic cell aggregate cultures. The GAG synthesized was predominantly CS and the hydrodynamic size of the newly synthesized chains was unchanged by SOX9 transduction. Aggrecan gene expression was increased in the SOX9-transduced chondrocytes and increased further in chondrogenic culture, but no comparable effects were found in SOX9 transduced dermal fibroblasts. However, the expression of CS glycosyltransferase and sulfotransferase genes in chondrocytes was unaffected by SOX9 transduction. Therefore SOX9 transduction in chondrocytes increased their CS synthetic capacity, but this was not accompanied by changes in the transcription of the CS biosynthetic enzymes and must occur by indirect regulation of enzyme activity through control of enzyme protein translation or enzyme organization.

译文

:转录因子SOX9(Sry型高迁移率族框9)在所有软骨细胞中表达,对于表达聚集蛋白聚糖至关重要,聚集蛋白聚糖在生物合成过程中被其重量的十倍以上的CS(硫酸软骨素)和软骨细胞分泌的软骨素形成软骨的特征性富含GAG(糖胺聚糖)的ECM(细胞外基质)。在分离的软骨细胞单层培养过程中,SOX9的表达迅速下降,从而关闭了聚集蛋白聚糖和相关CS合成。因此,我们研究了培养的人关节软骨细胞的SOX9转导是否对GAG生物合成所必需的糖基转移酶和磺基转移酶的基因表达有任何影响。传代软骨细胞的逆转录病毒SOX9转导提高了GAG合成的内源性速率,并提高了用β-木糖苷单层培养评估的GAG合成总容量。在软骨细胞聚集体培养中,GAG生物合成的内源速率和总容量都进一步增加。合成的GAG主要为CS,而新合成的链的流体动力学大小通过SOX9转导而没有改变。 Aggrecan基因表达在SOX9转导的软骨细胞中增加,并在软骨培养物中进一步增加,但是在SOX9转导的真皮成纤维细胞中未发现可比的效果。然而,CS糖基转移酶和磺基转移酶基因在软骨细胞中的表达不受SOX9转导的影响。因此,软骨细胞中SOX9的转导增加了CS的合成能力,但这并没有伴随CS生物合成酶的转录变化,必须通过控制酶蛋白翻译或酶组织间接调节酶活性来发生。

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