Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization.
Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization.
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DOI：
10.1016/j.jtbi.2011.06.016
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发表时间：
2011-09-21
影响因子：
2
通讯作者：
Mohler, George
中科院分区：
文献类型：
--
作者：
Ascenzi, Maria-Grazia;Blanco, Christian;Drayer, Ian;Kim, Hannah;Wilson, Ryan;Retting, Kelsey N.;Lyons, Karen M.;Mohler, George
本研究探讨了不动软骨细胞初级纤毛在生长板中的作用。这项研究的动机是（i）最近的证据表明，初级纤毛在肾小管上皮细胞的机械感觉功能;和（ii）不同的三维取向模式，软骨细胞初级纤毛形式在关节软骨中的存在或不存在的负载。对于我们的研究，我们使用Smad 1/5CKO突变小鼠，其生长板紊乱是由于Smad 1和5蛋白的条件性缺失，这些蛋白也影响所谓的印度刺猬途径，其物理和功能地形已被证明部分由初级纤毛控制。荧光和共聚焦显微镜染色切片可视化纤毛软骨细胞。收集有关软骨细胞的位置、方向和偏心率以及细胞膜上纤毛的定位、长度和方向的形态学数据，并从图像中重建。我们建立了纤毛的定位和方向是明确的，不同的，所以，在Smad 1/5CKO和对照小鼠。对于Smad 1/5CKO小鼠，初级纤毛相对于软骨细胞主轴的取向相对于前后方向成80°簇，显示对照小鼠中存在的10°额外簇的丧失。因此，我们假设在10°处的聚类包含柱状组织的信息。为了检验我们的假设，我们准备了一个数学模型的相对定位的增殖软骨细胞的人口纤毛方向的基础上。我们的模型属于“交互式粒子系统模型的自组织与出生”的范畴。该模型定性地再现了实验观察到的Smad 1/5CKO和对照小鼠的生长板中的软骨细胞排列。我们的数学预测的细胞分裂过程将需要进行实验观察，以推进纤毛功能的识别在生长板。
The research investigates the role of the immotile chondrocytic primary cilium in the growth plate. This study was motivated by (i) the recent evidence of the mechano-sensorial function of the primary cilium in kidney tubule epithelial cells; and (ii) the distinct three-dimensional orientation patterns that the chondrocytic primary cilium forms in articular cartilage in the presence or the absence of loading. For our investigation, we used the Smad1/5CKO mutant mouse, whose disorganized growth plate is due to the conditional deletion of Smad 1 and 5 proteins that also affect the so-called Indian Hedgehog pathway, whose physical and functional topography has been shown to be partially controlled by the primary cilium. Fluorescence and confocal microscopy on stained sections visualized ciliated chondrocytes. Morphometric data regarding position, orientation and eccentricity of chondrocytes, and ciliary localization on cell membrane, length and orientation, were collected and reconstructed from images. We established that both localization and orientation of the cilium are definite, and differently so, in the Smad1/5CKO and control mice. The orientation of the primary cilium, relative to the major axis of the chondrocyte, clusters at 80° with respect to the anterior-posterior direction for the Smad1/5CKO mice, showing loss of the additional clustering present in the control mice at 10°. We therefore hypothesized that the clustering at 10° contains information of columnar organization. To test our hypothesis, we prepared a mathematical model of relative positioning of the proliferative chondrocytic population based on ciliary orientation. Our model belongs to the category of “interactive particle system models for self-organization with birth”. The model qualitatively reproduced the experimentally observed chondrocytic arrangements in growth plate of each of the Smad1/5CKO and control mice. Our mathematically predicted cell division process will need to be observed experimentally to advance the identification of ciliary function in the growth plate.
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