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首页> 外文期刊>Cell and Tissue Research >Regulation of bone development and extracellular matrix protein genes by RUNX2.
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Regulation of bone development and extracellular matrix protein genes by RUNX2.

机译：RUNX2调节骨骼发育和细胞外基质蛋白基因。

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摘要

RUNX2 is a multifunctional transcription factor that controls skeletal development by regulating the differentiation of chondrocytes and osteoblasts and the expression of many extracellular matrix protein genes during chondrocyte and osteoblast differentiation. This transcription factor plays a major role at the late stage of chondrocyte differentiation: it is required for chondrocyte maturation and regulates Col10a1 expression in hypertrophic chondrocytes and the expression of Spp1, Ibsp, and Mmp13 in terminal hypertrophic chondrocytes. It is essential for the commitment of pluripotent mesenchymal cells to the osteoblast lineage. During osteoblast differentiation, RUNX2 upregulates the expression of bone matrix protein genes including Col1a1, Spp1, Ibsp, Bglap, and Fn1 in vitro and activates many promoters including those of Col1a1, Col1a2, Spp1, Bglap, and Mmp13. However, overexpression of Runx2 inhibits osteoblast maturation and reduces Col1a1 and Bglap expression. The inhibition of RUNX2 in mature osteoblasts does not reduce the expression of Col1a1 and Bglap in mice. Thus, RUNX2 directs pluripotent mesenchymal cells to the osteoblast lineage, triggers the expression of major bone matrix protein genes, and keeps the osteoblasts in an immature stage, but does not play a major role in the maintenance of the expression of Col1a1 or Bglap in mature osteoblasts. During bone development, RUNX2 induces osteoblast differentiation and increases the number of immature osteoblasts, which form immature bone, whereas Runx2 expression has to be downregulated for differentiation into mature osteoblasts, which form mature bone. During dentinogenesis, Runx2 expression is downregulated, and RUNX2 inhibits the terminal differentiation of odontoblasts.
机译：RUNX2是一种多功能转录因子，可通过调节软骨细胞和成骨细胞的分化以及软骨细胞和成骨细胞分化过程中许多细胞外基质蛋白基因的表达来控制骨骼发育。该转录因子在软骨细胞分化的晚期阶段起着重要作用：它是软骨细胞成熟所必需的，并调节肥大性软骨细胞中Col10a1的表达以及终末肥大性软骨细胞中Spp1，Ibsp和Mmp13的表达。对于多能间充质细胞向成骨细胞谱系的定位至关重要。在成骨细胞分化过程中，RUNX2在体外上调了包括Col1a1，Spp1，Ibsp，Bglap和Fn1的骨基质蛋白基因的表达，并激活了许多启动子，包括Col1a1，Col1a2，Spp1，Bglap和Mmp13的启动子。但是，Runx2的过表达抑制成骨细胞的成熟并降低Col1a1和Bglap的表达。在成骨细胞中抑制RUNX2不会降低小鼠中Col1a1和Bglap的表达。因此，RUNX2将多能间充质细胞定向到成骨细胞谱系，触发主要骨基质蛋白基因的表达，并使成骨细胞处于未成熟阶段，但在维持成熟的Col1a1或Bglap的表达中不发挥主要作用成骨细胞。在骨骼发育过程中，RUNX2诱导成骨细胞分化并增加形成未成熟骨骼的未成熟成骨细胞的数量，而Runx2表达必须下调才能分化为成熟成骨细胞，从而形成成熟骨骼。在牙本质生成过程中，Runx2表达下调，而RUNX2抑制成牙本质细胞的终末分化。

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