Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University, Stanford, California, United States of America.
PLoS One. 2007 Apr 25;2(4):e390. doi: 10.1371/journal.pone.0000390.
The majority of cells are equipped to detect and decipher physical stimuli, and then react to these stimuli in a cell type-specific manner. Ultimately, these cellular behaviors are synchronized to produce a tissue response, but how this is achieved remains enigmatic. Here, we investigated the genetic basis for mechanotransduction using the bone marrow as a model system. We found that physical stimuli produced a pattern of principal strain that precisely corresponded to the site-specific expression of sox9 and runx2, two transcription factors required for the commitment of stem cells to a skeletogenic lineage, and the arrangement and orientation of newly deposited type I collagen fibrils. To gain insights into the genetic basis for skeletal mechanotransduction we conditionally inactivated focal adhesion kinase (FAK), an intracellular component of the integrin signaling pathway. By doing so we abolished the mechanically induced osteogenic response and thus identified a critical genetic component of the molecular machinery required for mechanotransduction. Our data provide a new framework in which to consider how physical forces and molecular signals are synchronized during the program of skeletal regeneration.
大多数细胞都能够检测和解读物理刺激，然后以细胞类型特异性的方式对这些刺激做出反应。最终，这些细胞行为被同步以产生组织反应，但具体如何实现这一点仍然是个谜。在这里，我们使用骨髓作为模型系统来研究机械转导的遗传基础。我们发现，物理刺激产生了一种主应变模式，与 sox9 和 runx2 的特定表达位置精确对应，这两个转录因子是干细胞向成骨谱系分化所必需的，也是新沉积的 I 型胶原纤维的排列和取向所必需的。为了深入了解骨骼机械转导的遗传基础，我们条件性地使粘着斑激酶 (FAK)失活，FAK 是整合素信号通路的细胞内成分。通过这样做，我们消除了机械诱导的成骨反应，从而确定了机械转导所需的分子机制的关键遗传成分。我们的数据提供了一个新的框架，可以用来考虑在骨骼再生过程中物理力和分子信号是如何同步的。
