Liu Huanhuan, Zhang Can, Zhu Shouan, Lu Ping, Zhu Ting, Gong Xiaonan, Zhang Ziwang, Hu Jiajie, Yin Zi, Heng Boon Chin, Chen Xiao, Ouyang Hong Wei
Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, People's Republic of China.
Stem Cells. 2015 Feb;33(2):443-55. doi: 10.1002/stem.1866.
The transcription factor Mohawk (Mkx) is expressed in developing tendons and is an important regulator of tenogenic differentiation. However, the exact roles of Mkx in tendinopathy and tendon repair remain unclear. Using gene expression Omnibus datasets and immunofluorescence assays, we found that Mkx expression level was dramatically lower in human tendinopathy tissue and it is activated at specific stages of tendon development. In mesenchymal stem cells (MSCs), ectopic Mkx expression strikingly promoted tenogenesis more efficiently than Scleraxis (Scx), a well-known master transcription factor of tendon. Significantly higher levels of tenogenic gene expression and collagen fibril growth were observed with Mkx versus Scx. Interestingly, it was observed that Mkx dramatically upregulated Scx through binding to the Tgfb2 promoter. Additionally, the transplantation of Mkx-expressing-MSC sheets promoted tendon repair in a mouse model of Achilles-tendon defect. Taken together, these data shed light on previously unrecognized roles of Mkx in tendinopathy, tenogenesis, and tendon repair as well as in regulating the TGFβ pathway.
转录因子莫霍克（Mkx）在发育中的肌腱中表达，是肌腱分化的重要调节因子。然而，Mkx在肌腱病和肌腱修复中的具体作用仍不清楚。利用基因表达综合数据集和免疫荧光分析，我们发现Mkx在人类肌腱病组织中的表达水平显著降低，并且在肌腱发育的特定阶段被激活。在间充质干细胞（MSC）中，异位表达Mkx比著名的肌腱主转录因子硬骨素（Scx）更显著地促进肌腱生成。与Scx相比，Mkx处理后观察到肌腱生成相关基因表达水平和胶原纤维生长显著更高。有趣的是，发现Mkx通过与Tgfb2启动子结合显著上调Scx。此外，表达Mkx的MSC片移植促进了跟腱缺损小鼠模型中的肌腱修复。综上所述，这些数据揭示了Mkx在肌腱病、肌腱生成、肌腱修复以及调节TGFβ途径中以前未被认识的作用。
