Hata Kenji, Takahata Yoshifumi, Murakami Tomohiko, Nishimura Riko
Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
J Bone Metab. 2017 May;24(2):75-82. doi: 10.11005/jbm.2017.24.2.75. Epub 2017 May 31.
Endochondral ossification is the fundamental process of skeletal development in vertebrates. Chondrocytes undergo sequential steps of differentiation, including mesenchymal condensation, proliferation, hypertrophy, and mineralization. These steps, which are required for the morphological and functional changes in differentiating chondrocytes, are strictly regulated by a complex transcriptional network. Biochemical and mice genetic studies identified chondrogenic transcription factors critical for endochondral ossification. The transcription factor sex-determining region Y (SRY)-box 9 (Sox9) is essential for early chondrogenesis, and impaired Sox9 function causes severe chondrodysplasia in humans and mice. In addition, recent genome-wide chromatin immunoprecipitation-sequencing studies revealed the precise regulatory mechanism of Sox9 during early chondrogenesis. Runt-related transcription factor 2 promotes chondrocyte hypertrophy and terminal differentiation. Interestingly, endoplasmic reticulum (ER) stress-related transcription factors have recently emerged as novel regulators of chondrocyte differentiation. Here we review the transcriptional mechanisms that regulate endochondral ossification, with a focus on Sox9.
软骨内成骨是脊椎动物骨骼发育的基本过程。软骨细胞经历一系列分化步骤，包括间充质凝聚、增殖、肥大和矿化。这些步骤是分化中的软骨细胞形态和功能变化所必需的，受到一个复杂转录网络的严格调控。生化和小鼠遗传学研究确定了对软骨内成骨至关重要的软骨形成转录因子。转录因子性别决定区Y（SRY）-盒9（Sox9）对早期软骨形成至关重要，Sox9功能受损会导致人类和小鼠出现严重的软骨发育异常。此外，最近的全基因组染色质免疫沉淀测序研究揭示了Sox9在早期软骨形成过程中的精确调控机制。 runt相关转录因子2促进软骨细胞肥大和终末分化。有趣的是，内质网（ER）应激相关转录因子最近已成为软骨细胞分化的新型调节因子。在这里，我们综述了调节软骨内成骨的转录机制，重点是Sox9。
