Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development.
Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development.
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Mediator MED23与RUNX2合作驱动成骨细胞分化和骨骼发育
DOI：
10.1038/ncomms11149
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发表时间：
2016-04-01
影响因子：
16.6
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Liu Z;Yao X;Yan G;Xu Y;Yan J;Zou W;Wang G
在发育过程中谱系特异性是如何调节的是一个突出的问题，成骨因子RUNX 2的分子调节仍有待充分理解。在此我们报道了Mediator亚基MED 23与RUNX 2共同调控成骨细胞的分化和骨发育。Med 23在间充质干细胞或成骨细胞前体中的缺失导致了与Runx 2 +/−小鼠相似的多种骨缺损。在体外，Med 23缺失的祖细胞难以向成骨细胞分化，Med 23缺失降低了Runx 2靶基因的活性而不改变Runx 2的表达。在机制上，MED 23结合RUNX 2并调节其转录活性。此外，骨祖细胞中的Med 23缺陷加剧了Runx 2 +/−小鼠中观察到的骨骼异常。总的来说，我们的研究结果建立了RUNX 2和MED 23之间的遗传和物理相互作用，表明MED 23构成了合成代谢骨形成和相关疾病调控网络中的分子节点。
How lineage specifiers are regulated during development is an outstanding question, and the molecular regulation of osteogenic factor RUNX2 remains to be fully understood. Here we report that the Mediator subunit MED23 cooperates with RUNX2 to regulate osteoblast differentiation and bone development.Med23deletion in mesenchymal stem cells or osteoblast precursors results in multiple bone defects similar to those observed inRunx2+/−mice.In vitro,Med23-deficient progenitor cells are refractory to osteoblast differentiation, andMed23deficiency reducesRunx2-target gene activity without changing Runx2 expression. Mechanistically, MED23 binds to RUNX2 and modulates its transcriptional activity. Moreover,Med23deficiency in osteoprogenitor cells exacerbates the skeletal abnormalities observed inRunx2+/−mice. Collectively, our results establish a genetic and physical interaction between RUNX2 and MED23, suggesting that MED23 constitutes a molecular node in the regulatory network of anabolic bone formation and related diseases.