转录中介体是由进化上保守的多蛋白质组成的复合体，在发育和环境信号的刺激下,受转录因子招募而参与基因的转录。我们目前发现转录中介体亚基MED23在成骨分化和骨发育中发挥着重要的作用。在间充质干细胞或成骨细胞前体中敲除Med23，小鼠出现颅骨卤门闭合延迟、锁骨短小、骨质减少等异常骨发育表型，这种表型与一种称为颅骨锁骨发育不全综合症(CCD)的人类骨发育疾病病症高度相似。在体外诱导成骨细胞分化实验中，缺失Med23的前体细胞向成骨分化的能力受到抑制。基因表达分析显示Med23缺失抑制成骨分化特异的标志基因，但不影响关键转录因子Runx2的表达。这些结果表明Med23是成骨分化及骨发育过程中的一个重要调控因子。本申请拟深入研究MED23在成骨发育中的功能和分子机制，解析成骨发育的分子调控网络，加深理解骨发育相关疾病尤其是CCD的发病机理，为预防和治疗提供理论知识。

Mediator complex is an evolutionarily conserved transcriptional cofactor complex that is recruited by transcriptional factors to control diverse gene programs in response to developmental or environmental signals. We now find that Mediator subunit MED23 plays an indispensable role in osteoblast differentiation and bone development. Ablation of Med23 at different developmental stages (in mesenchymal stem cells or osteoblast precursors) leads to delay in the closure of fontanel bone, short clavicles and decreased bone mass in mice, which is very similar with the phenotype of the cleidocranial dysplasia (CCD), a human bone disease. In addition, in vitro osteogenic experiment shows that Med23-dificient progenitor cells are refractory to differentiate into osteoblasts. Gene expression analysis reveals that Med23 deficiency doesn't affect expression of Runx2, but reduces expression of its downstream genes. These results suggest that MED23 is a novel important molecular for osteoblast differentiation and bone development. We attempt to explore the mechanism by which how MED23 regulate osteogenic differentiation and bone development, and to enhance our understanding of the regulation network for bone development and related diseases. These efforts may constitute a theoretical basis for prevention and treatment.