Role of KLF4 during skeletal development

Kruppel-like factor 4（KLF4/ GKLF/ EZF）是一种锌指型转录因子，在皮肤、肠、睾丸、肺和骨中高度表达。它在骨细胞中的作用尚不清楚。为了研究Klf4在骨骼发育过程中可能发挥的作用，我们在小鼠I型胶原蛋白调控序列下产生了表达Klf4的转基因小鼠。转基因小鼠颅骨形成延迟；在培养的原代小鼠颅骨成骨细胞中过表达Klf4导致矿化抑制，表明Klf4的调节是通过成骨细胞自主作用。令人惊讶的是，转基因小鼠的长骨表现出骨髓腔形成的延迟。我们的研究结果表明Klf4通过协调成骨细胞、软骨细胞、血管内皮细胞和破骨细胞的分化和迁移来调节正常的骨骼发育。

Kruppel-like factor 4(KLF4/ GKLF/ EZF) is a zinc finger type of transcription factor highly expressed in the skin, intestine, testis, lung and bone. Its role in bone cells is unknown. To investigate the possible roles played by Klf4 during skeletal development, we generated transgenicmice expressing Klf4 under mouse type I collagen regulatory sequence. Transgenic mice showed delayed formation of the calvarial bones ; and over-expressing Klf4 in primary mouse calvarial osteoblasts in culture resulted in repression of mineralization indicating that this regulation of Klf4 is through an osteoblast-autonomous effect. Surprisingly, long bones of the transgenicmice exhibited delayed marrowcavity formation. Our results demonstrate that Klf4 regulates normal skeletal development through coordinating the differentiation and migration of osteoblasts, chondrocytes, vascular endothelial cells and osteoclasts.