Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels
Dendritic processes of osteocytes are mechanotransducers that induce the opening of hemichannels
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DOI：
10.1073/pnas.1009382107
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发表时间：
2010-08-03
影响因子：
11.1
通讯作者：
Jiang, Jean X.
中科院分区：
文献类型：
--
作者：
Burra, Sirisha;Nicolella, Daniel P.;Jiang, Jean X.
已知具有长树突状突起的骨细胞能够感知机械负荷，这对于骨重塑至关重要。关于骨细胞的哪一部分（细胞体与树突突）充当机械传感器，一直存在争论。为了通过实验解决这个问题，我们使用了跨孔过滤系统来区分细胞体和树突状过程。对细胞体或树突施加机械负荷，并通过连接蛋白 43 半通道开口观察骨细胞的反应。当对树突或细胞体施加机械负荷时，位于细胞体上的半通道被诱导打开。然而，当细胞的任一部分受到机械刺激时，没有检测到树突中显着的半通道活性。透明质酸酶仅在树突侧破坏糖萼就足以减弱树突诱导细胞体上半通道打开的能力，而透明质酸酶在应用于细胞体时没有这种效果。重要的是，对树突侧的透明质酸酶处理导致形成较差的整合素附着物，并且树突在transwell过滤器的下侧形成整合素附着物的能力降低。总之，我们的研究表明，骨细胞树突状过程的糖萼是形成强整合素附着所必需的。这些整合素附着物可能充当机械传感器，将机械信号传递到细胞体，导致半通道打开，从而允许快速交换对骨重塑重要的因子。
Osteocytes with long dendritic processes are known to sense mechanical loading, which is essential for bone remodeling. There has been a long-standing debate with regard to which part(s) of osteocyte, the cell body versus the dendritic process, acts as a mechanical sensor. To address this question experimentally, we used a transwell filter system that differentiates the cell body from the dendritic processes. Mechanical loading was applied to either the cell body or the dendrites, and the osteocyte's response was observed through connexin 43 hemichannel opening. The hemichannels located on the cell body were induced to open when mechanical loading was applied to either the dendritic processes or the cell body. However, no significant hemichannel activity in the dendrites was detected when either part of the cell was mechanically stimulated. Disruption of the glycocalyx by hyaluronidase on the dendrite side alone is sufficient to diminish a dendrite's ability to induce the opening of hemichannels on the cell body, while hyaluronidase has no such effect when applied to the cell body. Importantly, hyaluronidase treatment to the dendrite side resulted in formation of poor integrin attachments with the reduced ability of the dendrites to form integrin attachments on the underside of the transwell filter. Together, our study suggests that the glycocalyx of the osteocyte dendritic process is required for forming strong integrin attachments. These integrin attachments probably serve as the mechanotransducers that transmit the mechanical signals to the cell body leading to the opening of hemichannels, which permits rapid exchange of factors important for bone remodeling.