Roles of Runx2 in Skeletal Development
Roles of Runx2 in Skeletal Development
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DOI：
10.1007/978-981-10-3233-2_6
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发表时间：
2017-01-01
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影响因子：
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通讯作者：
Komori, Toshihisa
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作者：
Komori, Toshihisa
Runx 2是成骨细胞分化所必需的最上游转录因子。它调节Sp 7的表达，Sp 7的蛋白质是成骨细胞分化的关键转录因子，以及骨基质基因包括Spp 1，Ibsp和Bglap 2的表达。Runx 2也是软骨细胞成熟所必需的，Runx 3在软骨细胞成熟中与Runx 2具有冗余功能。Runx 2调节软骨细胞中Col 10a 1、Spp 1、Ibsp和Mmp 13的表达。它还抑制软骨细胞获得永久性软骨软骨细胞的表型。它通过调节Ihh表达来调节软骨细胞增殖。Runx 2通过调节Rankl增强破骨细胞生成。Cbfb是Runx家族蛋白的共转录因子，通过稳定Runx家族蛋白在骨骼发育中起重要作用。在Cbfb同种型中，Cbfb 1在Runx 2依赖性转录调控中比Cbfb 2更有效;然而，Cbfb 2的表达水平比Cbfb 1高3倍，表明在骨骼发育中需要Cbfb 2。Runx 2在成骨细胞中的表达受位于P1启动子上游的343 bp增强子调控。该增强子由Dlx 5/6、Mef 2、Tcf 7、Ctnnb 1、Sox 5/6、Smad 1和Sp 7组成的增强体激活。因此，Runx 2是骨骼发育所必需的多功能转录因子，Cbfb通过调节Runx家族蛋白的稳定性和转录活性来调节骨骼发育。
Runx2 is the most upstream transcription factor essential for osteoblast differentiation. It regulates the expression of Sp7, the protein of which is a crucial transcription factor for osteoblast differentiation, as well as that of bone matrix genes including Spp1, Ibsp, and Bglap2. Runx2 is also required for chondrocyte maturation, and Runx3 has a redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the expression of Col10a1, Spp1, Ibsp, and Mmp13 in chondrocytes. It also inhibits chondrocytes from acquiring the phenotypes of permanent cartilage chondrocytes. It regulates chondrocyte proliferation through the regulation of Ihh expression. Runx2 enhances osteoclastogenesis by regulating Rankl. Cbfb, which is a co-transcription factor for Runx family proteins, plays an important role in skeletal development by stabilizing Runx family proteins. In Cbfb isoforms, Cbfb1 is more potent than Cbfb2 in Runx2-dependent transcriptional regulation; however, the expression level of Cbfb2 is three-fold higher than that of Cbfb1, demonstrating the requirement of Cbfb2 in skeletal development. The expression of Runx2 in osteoblasts is regulated by a 343-bp enhancer located upstream of the P1 promoter. This enhancer is activated by an enhanceosome composed of Dlx5/6, Mef2, Tcf7, Ctnnb1, Sox5/6, Smad1, and Sp7. Thus, Runx2 is a multifunctional transcription factor that is essential for skeletal development, and Cbfb regulates skeletal development by modulating the stability and transcriptional activity of Runx family proteins.