Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes.

Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes.
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力和巩膜协同促进人 ES 细胞衍生的 MSC 向肌腱细胞的定向

DOI:
10.1038/srep00977
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Ouyang, Hong-wei
Ouyang, Hong-wei
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen, Xiao;Yin, Zi;Chen, Jia-lin;Shen, Wei-liang;Liu, Huan-huan;Tang, Qiao-mei;Fang, Zhi;Lu, Lin-rong;Ji, Junfeng;Ouyang, Hong-wei

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由于肌腱干/祖细胞在肌腱组织中的数量很少,肌腱作为运动损伤的易损伤靶点,其自我修复能力较差。人胚胎干细胞(hESCs)是肌腱再生的一种有前途的方法。但他们的teno-lineage分化策略尚未确定。在这里,我们报告说,力与肌腱特异性转录因子scleraxis协同促进承诺的hESC肌腱细胞的功能性组织再生。力和巩膜轴可以独立地诱导肌腱分化。然而,单独的力伴随着激活成骨,而单独的巩膜不足以提交,但增加肌腱分化。巩膜轴通过拮抗BMP信号通路,协同增强力对肌腱向骨分化的影响,抑制骨向骨分化。这些发现不仅证明了一种新的策略,指导hESC分化为肌腱细胞的功能性肌腱再生,但也提供了深入了解力,scleraxis和bmp 2控制肌腱谱系分化的网络。
As tendon stem/progenitor cells were reported to be rare in tendon tissues, tendons as vulnerable targets of sports injury possess poor self-repair capability. Human ESCs (hESCs) represent a promising approach to tendon regeneration. But their teno-lineage differentiation strategy has yet to be defined. Here, we report that force combined with the tendon-specific transcription factor scleraxis synergistically promoted commitment of hESCs to tenocyte for functional tissue regeneration. Force and scleraxis can independently induce tendon differentiation. However, force alone concomitantly activated osteogenesis, while scleraxis alone was not sufficient to commit, but augment tendon differentiation. Scleraxis synergistically augmented the efficacy of force on teno-lineage differentiation and inhibited the osteo-lineage differentiation by antagonized BMP signaling cascade. The findings not only demonstrated a novel strategy of directing hESC differentiation to tenocyte for functional tendon regeneration, but also offered insights into understanding the network of force, scleraxis and bmp2 controlling tendon-lineage differentiation.
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