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首页> 外文期刊>Journal of Cellular Physiology >The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis.
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The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis.

机译：的硫酸乙酰肝素蛋白聚糖(HSPG) glypican-3细胞介导的承诺MC3T3-E1方向骨生成。

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Heparan sulfate (HS) sugar chains attached to core proteoglycans (PGs) termed HSPGs mediate an extensive range of cell-extracellular matrix (ECM) and growth factor interactions based upon their sulfation patterns. When compared with non-osteogenic (maintenance media) culture conditions, under established osteogenic culture conditions, MC3T3-E1 cells characteristically increase their osteogenic gene expression profile and switch their dominant fibroblast growth factor receptor (FGFR) from FGFR1 (0.5-fold decrease) to FGFR3 (1.5-fold increase). The change in FGFR expression profile of the osteogenic-committed cultures was reflected by their inability to sustain an FGF-2 stimulus, but respond to BMP-2 at day 14 of culture. The osteogenic cultures decreased their chondroitin and dermatan sulfate PGs (biglycan, decorin, and versican), but increased levels of the HS core protein gene expression, in particular glypican-3. Commitment and progress through osteogenesis is accompanied by changes in FGFR expression, decreased GAG initiation but increased N- and O-sulfation and reduced remodeling of the ECM (decreased heparanase expression) resulting in the production of homogenous (21 kDa) HS chain. With the HSPG glypican-3 expression strongly upregulated in these processes, siRNA was used to knockdown this gene to examine the effect on osteogenic commitment. Reduced glypican-3 abrogated the expression of Runx2, and thus differentiation. The reintroduction of this HSPG into Runx2-null cells allowed osteogenesis to proceed. These results demonstrate the dependence of osteogenesis on specific HS chains, in particular those associated with glypican-3.
机译：硫酸乙酰肝素(HS)糖链连接到核心蛋白聚糖(后卫)称为HSPGs调解广泛范围的cell-extracellular矩阵(ECM)和基于生长因子相互作用他们的硫酸盐化作用模式。non-osteogenic(维护媒体)文化下条件,建立成骨的文化条件下,典型MC3T3-E1细胞增加成骨基因表达谱和开关主要纤维母细胞生长因子受体(FGFR) FGFR1(0.5倍减少)FGFR3(增加1.5倍)。FGFR表达谱的变化osteogenic-committed文化反映了他们无法维持FGF-2刺激,但是应对BMP-2 14天的文化。减少他们的软骨素成骨的文化而且硫酸dermatan后卫(实验、decorin和versican),但增加HS核心的水平特别是蛋白质基因表达glypican-3。骨生成伴随着FGFR的变化表达,减少呕吐开始增加N - O-sulfation和减少ECM重塑(heparanase下降表达式)导致的生产同质(kDa 21日)商品链。glypican-3表达强烈的调节这些过程,siRNA用于击倒基因检查对成骨的影响的承诺。Runx2的表达,从而分化。的重新引入这个HSPG Runx2-null骨生成细胞允许继续。结果验证的依赖骨生成特定商品链,特别是那些与glypican-3有关。

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