Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Cell Tissue Res. 2010 Jan;339(1):189-95. doi: 10.1007/s00441-009-0832-8. Epub 2009 Aug 1.
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.
RUNX2 是一种多功能转录因子，通过调节软骨细胞和骨细胞的分化以及软骨细胞和骨细胞分化过程中许多细胞外基质蛋白基因的表达，控制骨骼发育。这种转录因子在软骨细胞分化的晚期起着主要作用：它是软骨细胞成熟所必需的，调节肥大软骨细胞中 Col10a1 的表达以及终末肥大软骨细胞中 Spp1、Ibsp 和 Mmp13 的表达。它对于多能间充质细胞向成骨细胞谱系的定向分化是必不可少的。在成骨细胞分化过程中，RUNX2 上调 Col1a1、Spp1、Ibsp、Bglap 和 Fn1 等骨基质蛋白基因的表达，并激活包括 Col1a1、Col1a2、Spp1、Bglap 和 Mmp13 在内的许多启动子。然而，Runx2 的过表达抑制成骨细胞的成熟并降低 Col1a1 和 Bglap 的表达。在成熟的成骨细胞中抑制 RUNX2 并不减少 Col1a1 和 Bglap 在小鼠中的表达。因此，RUNX2 指导多能间充质细胞向成骨细胞谱系分化，触发主要骨基质蛋白基因的表达，并使成骨细胞保持在未成熟阶段，但在成熟成骨细胞中 Col1a1 或 Bglap 的表达维持中不起主要作用。在骨发育过程中，RUNX2 诱导成骨细胞分化并增加未成熟成骨细胞的数量，这些细胞形成未成熟骨，而 Runx2 的表达必须下调以分化为成熟成骨细胞，这些细胞形成成熟骨。在牙本质形成过程中，Runx2 的表达下调，RUNX2 抑制成牙本质细胞的终末分化。
