Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism
Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism
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DOI：
10.1096/fj.15-276402
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发表时间：
2016-04-01
期刊：
影响因子：
4.8
通讯作者：
Jacobs, Christopher R.
中科院分区：
文献类型：
--
作者：
Chen, Julia C.;Hoey, David A.;Jacobs, Christopher R.
长期以来，人们一直怀疑，但从未直接表明，骨形成以适应机械负荷的增加与骨骼干细胞成骨细胞的产生有关。事实上，生物物理刺激在体外有效地调节成骨谱系定型。在这项研究中，我们移植了表达绿色荧光蛋白的骨髓细胞，使谱系追踪成为可能，并使小鼠受到生物物理刺激，以引起骨形成反应。我们检测到来源于移植祖细胞的细胞嵌入在骨基质中，靠近活性骨形成表面，以响应载荷，首次证明，机械信号增强骨髓细胞归巢和附着到骨表面，并承诺这些细胞在体内的成骨谱系。此外，我们使用了一个诱导型Cre/Lox重组系统删除驱动蛋白家族成员3A（Kif 3a），一个基因，是必要的初级纤毛形成，在移植细胞及其后代中，无论哪种组织可能已纳入他们。破坏的mechanosensing细胞器，在一个祖人口的主要纤毛，显着减少了骨形成的数量在响应机械刺激。我们研究的集体结果直接表明，在一种新的实验干细胞机械生物学模型中，机械信号增强了体内成骨谱系的定型，并且初级纤毛有助于这一过程。Chen，J.C.，Hoey，D.一、Chua，M.，贝隆河雅各布斯角R.机械信号通过初级纤毛介导的机制促进成骨命运。FASEB J.30，1504-1511（2016）. www.fasebj.org
It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitment in vitro. In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for thefirst time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cells in vivo. Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitment in vivo and that the primary cilium contributes to this process.-Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. FASEB J. 30, 1504-1511 (2016). www.fasebj.org