Integrative Study of transcriptional network systems during enchondral ossification

软骨成骨是一种非常独特和复杂的生物事件，它受到多种生长因子和细胞因子的协调而严格的调控。这些因子通过控制细胞内信号和转录因子来调节软骨细胞的成骨。转录因子Sox9和Runx2在软骨成骨中起重要作用。我们发现，在软骨成骨过程中，p54^&lt；nrb&gt；通过与Sox9形成转录复合体，将转录与mRNA成熟结合起来。相反，与Sox9形成转录复合体的Arid5a和Znf219在与Sox9相关的软骨细胞分化中发挥作用。此外，我们还发现Sox9通过上调PTHrP的表达，在软骨形成的后期与IHH/Gli信号形成负反馈环。此外，我们还发现一个转录因子Dmrt2将Sox9的功能与Runx2联系起来。总而言之，我们的发现为软骨骨化的分子基础提供了新的见解。

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.