Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin.
Embryonic mechanical and soluble cues regulate tendon progenitor cell gene expression as a function of developmental stage and anatomical origin.
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DOI：
10.1016/j.jbiomech.2013.09.018
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发表时间：
2014-01-03
影响因子：
2.4
通讯作者：
Kuo CK
中科院分区：
文献类型：
--
作者：
Brown JP;Finley VG;Kuo CK
基于干细胞的肌腱工程策略尚未产生正常的功能性组织，部分原因是需要腱生成因子。此外，由于缺乏分化标志物，评估分化的能力受到了挑战。我们提议利用参与正常组织形成的发育线索以及作为分化的肌腱祖细胞（TPCs）特征的表型标志物来为肌腱再生提供信息。机械力、成纤维细胞生长因子（FGF）-4和转化生长因子（TGF）-β2与胚胎肌腱发育有关，但这些因子对分化的TPCs的单独作用尚不清楚。此外，肢体肌腱和轴性肌腱的发育机制不同，这表明各自的细胞类型被设定为对外源因子有独特的反应。为了描述向肢体与轴性表型分化的发育线索和基准，我们对TPCs进行动态加载并用生长因子处理，评估基因表达谱作为发育阶段和解剖来源的函数。基于硬腱蛋白聚糖（scleraxis）表达，TGFβ2在所有阶段对TPCs都有腱生成作用，而加载仅对晚期细胞有作用，FGF4尽管对其他基因有调节作用但没有效果。当因子组合时，TGFβ2继续有腱生成作用，而FGF4似乎有抗腱生成作用。各种处理引起特定阶段的轴性与肢体TPCs的不同反应。这些结果确定了腱生成因子，表明肌腱工程策略应根据解剖来源为组织定制，并提供肢体和轴性TPCs的特定阶段基因表达谱作为监测干细胞腱生成分化的基准。
Stem cell-based engineering strategies for tendons have yet to yield a normal functional tissue, due in part to a need for tenogenic factors. Additionally, the ability to evaluate differentiation has been challenged by a lack of markers for differentiation. We propose to inform tendon regeneration with developmental cues involved in normal tissue formation and with phenotypic markers that are characteristic of differentiating tendon progenitor cells (TPCs). Mechanical forces, fibroblast growth factor (FGF)-4 and transforming growth factor (TGF)-β2 are implicated in embryonic tendon development, yet the isolated effects of these factors on differentiating TPCs are unknown. Additionally, developmental mechanisms vary between limb and axial tendons, suggesting the respective cell types are programmed to respond uniquely to exogenous factors. To characterize developmental cues and benchmarks for differentiation toward limb vs. axial phenotypes, we dynamically loaded and treated TPCs with growth factors and assessed gene expression profiles as a function of developmental stage and anatomical origin. Based on scleraxis expression, TGFβ2 was tenogenic for TPCs at all stages, while loading was for late-stage cells only, and FGF4 had no effect despite regulation of other genes. When factors were combined, TGF 2 continued to be tenogenic, while FGF4 appeared anti-tenogenic. Various treatments elicited distinct responses by axial vs. limb TPCs of specific stages. These results identified tenogenic factors, suggest tendon engineering strategies should be customized for tissues by anatomical origin, and provide stage-specific gene expression profiles of limb and axial TPCs as benchmarks with which to monitor tenogenic differentiation of stem cells.
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影响因子：
4.8
作者：
Lorda-Diez, Carlos I.;Montero, Juan A.;Hurle, Juan M.
通讯作者：
Hurle, Juan M.
影响因子：
4.6
作者：
Pryce, Brian A.;Watson, Spencer S.;Schweitzer, Ronen
通讯作者：
Schweitzer, Ronen
影响因子：
4.6
作者：
Murchison, Nicholas D.;Price, Brian A.;Schweitzer, Ronen
通讯作者：
Schweitzer, Ronen
影响因子：
2.2
作者：
KODAMA, N;SEKIGUCHI, S
通讯作者：
SEKIGUCHI, S
影响因子：
4.1
作者：
Kuo, Catherine K.;Tuan, Rocky S.
通讯作者：
Tuan, Rocky S.