Integrative Study of transcriptional network systems during enchondral ossification

软骨骨化是一个非常独特而复杂的生物学过程，它受到多种生长因子和细胞因子的协调和严格调控。这些因子通过控制细胞内信号传导和转录因子来调节内软骨骨化。转录因子Sox 9和Runx 2在软骨骨化中起重要作用。我们发现p54<nrb>通过与Sox 9形成转录复合物，在软骨骨化过程中将转录与mRNA成熟偶联。与此相反，Arid 5a和Znf 219都与Sox 9形成转录复合物，在与Sox 9相关的软骨细胞分化中发挥作用。此外，我们发现Sox 9通过上调PTHrP的表达与Ihh/Gli信号形成负反馈环，用于软骨形成的晚期阶段。此外，我们确定了一个转录因子，Dmrt 2，链接Sox 9功能Runx 2。总的来说，我们的研究结果提供了新的见解的分子基础的enchoniossification。

Enchondral ossification is very unique and complex biological event which is harmoniously and strictly regulated by several growth factors and cytokines. These factors regulate enchondral ossification by controlling intracellular signaling and transcription factors. Transcription factors, Sox9 and Runx2, play essential roles in enchondral ossification. We found that p54^<nrb> couples transcription to mRNA maturation during enchondral ossification by forming transcriptional complex with Sox9. In contrast, Arid5a and Znf219, both of which form transcriptional complex with Sox9, play a role in chondrocyte differentiation in association with Sox9. In addition, we found that Sox9 forms negative-feedback loop with Ihh/Gli signaling for late stage of chondrogenesis by up-regulating PTHrP expression. Furthermore, we identified that a transcription factor, Dmrt2, links Sox9 function to Runx2. Collectively, our findings provide novel insights into molecular basis of enchondral ossification.