Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
Int J Mol Sci. 2019 Apr 4;20(7):1694. doi: 10.3390/ijms20071694.
Runx2 is essential for osteoblast differentiation and chondrocyte maturation. During osteoblast differentiation, Runx2 is weakly expressed in uncommitted mesenchymal cells, and its expression is upregulated in preosteoblasts, reaches the maximal level in immature osteoblasts, and is down-regulated in mature osteoblasts. Runx2 enhances the proliferation of osteoblast progenitors by directly regulating and . Runx2 enhances the proliferation of suture mesenchymal cells and induces their commitment into osteoblast lineage cells through the direct regulation of hedgehog (, , and ), Fgf ( and ), Wnt (, , and ), and Pthlh () signaling pathway genes, and . heterozygous mutation causes open fontanelle and sutures because more than half of the gene dosage is required for the induction of these genes in suture mesenchymal cells. Runx2 regulates the proliferation of osteoblast progenitors and their differentiation into osteoblasts via reciprocal regulation with hedgehog, Fgf, Wnt, and Pthlh signaling molecules, and transcription factors, including Dlx5 and Sp7. Runx2 induces the expression of major bone matrix protein genes, including , , , , and , in vitro. However, the functions of Runx2 in differentiated osteoblasts in the expression of these genes in vivo require further investigation.
Runx2 对于成骨细胞分化和软骨细胞成熟是必需的。在成骨细胞分化过程中，Runx2 在未定向的间充质细胞中弱表达，在成骨前体细胞中其表达上调，在未成熟的成骨细胞中达到最高水平，并在成熟的成骨细胞中下调。Runx2 通过直接调节 和 来增强成骨细胞前体的增殖。Runx2 通过直接调节 hedgehog（ 、 和 ）、Fgf（ 和 ）、Wnt（ 、 和 ）和 Pthlh（ ）信号通路基因，以及 ，来增强缝间间充质细胞的增殖，并诱导其向成骨细胞谱系细胞分化。Runx2 杂合突变导致囟门和骨缝开放，因为在缝间间充质细胞中诱导这些基因表达需要超过一半的 基因剂量。Runx2 通过与 hedgehog、Fgf、Wnt 和 Pthlh 信号分子以及转录因子（包括 Dlx5 和 Sp7）的相互调节，调节成骨细胞前体的增殖及其分化为成骨细胞。Runx2 在体外诱导主要骨基质蛋白基因的表达，包括 、 、 、 和 。然而，Runx2 在体内分化的成骨细胞中这些基因的表达的功能需要进一步研究。
