Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions
Mechanically stimulated osteocytes regulate osteoblastic activity via gap junctions
复制标题
DOI：
10.1152/ajpcell.00611.2005
复制
发表时间：
2007-01-01
影响因子：
5.5
通讯作者：
Donahue, H. J.
中科院分区：
文献类型：
--
作者：
Taylor, A. F.;Saunders, M. M.;Donahue, H. J.
骨的结构特性与其所经受的机械力之间的强相关性长期以来一直归因于细胞的存在，该细胞不仅检测机械负荷，而且在结构上适应骨基质以对抗机械负荷。这种“机械稳定器”最可能的细胞候选者之一是骨细胞，其位于矿化的骨基质内，并且完全位于检测机械诱导的信号的位置。然而，由于骨细胞既不能形成骨也不能再吸收骨，因此假设它们通过协调驻留在骨表面上的细胞（如成骨细胞）的作用来协调机械诱导的骨重建。为了研究这个假设，我们开发了一种新的骨细胞-成骨细胞共培养模型，通过允许我们将骨细胞暴露于生理水平的流体剪切力，同时将成骨细胞屏蔽于流体剪切力，来模拟体内系统。我们的研究结果表明，暴露于4.4 dyn/cm（2）的流体剪切力的骨细胞迅速增加了被屏蔽的成骨细胞的碱性磷酸酶活性，并且骨细胞-成骨细胞共培养模型中的成骨细胞-成骨细胞共培养模型中的成成骨细胞的物理接触是先决条件。此外，功能性间隙连接细胞间通讯和丝裂原活化蛋白激酶、细胞外信号调节激酶1/2信号通路是成骨细胞对骨细胞通讯机械信号反应的重要组成部分。通过利用其他nonosteocyte共培养模型，我们还表明，介导成骨细胞碱性磷酸酶水平的能力，在流体剪切的应用是一种独特的现象，骨细胞和其他间充质细胞类型不能复制。
The strong correlation between a bone's architectural properties and the mechanical forces that it experiences has long been attributed to the existence of a cell that not only detects mechanical load but also structurally adapts the bone matrix to counter it. One of the most likely cellular candidates for such a "mechanostat" is the osteocyte, which resides within the mineralized bone matrix and is perfectly situated to detect mechanically induced signals. However, as osteocytes can neither form nor resorb bone, it has been hypothesized that they orchestrate mechanically induced bone remodeling by coordinating the actions of cells residing on the bone surface, such as osteoblasts. To investigate this hypothesis, we developed a novel osteocyte-osteoblast coculture model that mimics in vivo systems by permitting us to expose osteocytes to physiological levels of fluid shear while shielding osteoblasts from it. Our results show that osteocytes exposed to a fluid shear rate of 4.4 dyn/cm(2) rapidly increase the alkaline phosphatase activity of the shielded osteoblasts and that osteocytic-osteoblastic physical contact is a prerequisite. Furthermore, both functional gap junctional intercellular communication and the mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 signaling pathway are essential components in the osteoblastic response to osteocyte communicated mechanical signals. By utilizing other nonosteocytic coculture models, we also show that the ability to mediate osteoblastic alkaline phosphatase levels in response to the application of fluid shear is a phenomena unique to osteocytes and is not reproduced by other mesenchymal cell types.