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Substrate Adhesion Regulates Sealing Zone Architecture and Dynamics in Cultured Osteoclasts

机译:基质粘附力调节培养破骨细胞的密封区结构和动力学。

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摘要

The bone-degrading activity of osteoclasts depends on the formation of a cytoskeletal-adhesive super-structure known as the sealing zone (SZ). The SZ is a dynamic structure, consisting of a condensed array of podosomes, the elementary adhesion-mediating structures of osteoclasts, interconnected by F-actin filaments. The molecular composition and structure of the SZ were extensively investigated, yet despite its major importance for bone formation and remodelling, the mechanisms underlying its assembly and dynamics are still poorly understood. Here we determine the relations between matrix adhesiveness and the formation, stability and expansion of the SZ. By growing differentiated osteoclasts on micro-patterned glass substrates, where adhesive areas are separated by non-adhesive PLL-g-PEG barriers, we show that SZ growth and fusion strictly depend on the continuity of substrate adhesiveness, at the micrometer scale. We present a possible model for the role of mechanical forces in SZ formation and reorganization, inspired by the current data.
机译:破骨细胞的骨降解活性取决于被称为密封区(SZ)的细胞骨架粘附性超结构的形成。 SZ是一种动态结构,由浓缩的足小体阵列(破骨细胞的基本粘附介导结构)组成,并通过F-肌动蛋白丝相互连接。尽管对SZ的分子组成和结构进行了广泛的研究,但是尽管SZ对于骨骼形成和重塑非常重要,但对其组装和动力学的机制仍知之甚少。在这里,我们确定基质粘合性与SZ的形成,稳定性和膨胀之间的关系。通过在微图案化的玻璃基板上生长差异化的破骨细胞,其中胶粘剂区域被非胶粘剂PLL-g-PEG屏障隔开,我们显示出SZ的生长和融合在微米尺度上严格取决于基板胶粘剂的连续性。在当前数据的启发下,我们提出了机械力在SZ形成和重组中的作用的可能模型。

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