Mechanical strain affects dura mater biological processes: Implications for immature calvarial healing
Mechanical strain affects dura mater biological processes: Implications for immature calvarial healing
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DOI：
10.1097/01.prs.0000079860.14734.d6
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发表时间：
2003-10-01
影响因子：
3.6
通讯作者：
Longaker, MT
中科院分区：
文献类型：
--
作者：
Fong, KD;Warren, SM;Longaker, MT
人的大脑在生命的头两年里生长迅速。这种生长会在覆盖的硬脑膜和脑颅中产生张拉应变。有趣的是，婴儿很大程度上是在这两年的生长期内，能够重新骨化颅骨缺陷。这一临床观察很重要，因为它表明，在活跃的颅内容量扩张期间，颅骨愈合最强劲。在大鼠模型中，先前已经证明，未成熟的硬脑膜比成熟的硬脑膜增殖更快，并产生更多的成骨细胞因子和成骨细胞分化的标志。因此，假设生长中的大脑产生的机械应变会诱导未成熟的硬脑膜增殖，并增加颅骨生长和愈合所必需的成骨细胞因子的表达。人和大鼠(n=40)的颅内体积扩张被计算为年龄的函数。这些计算表明，人类83%的颅内体积扩张是在2岁时完成的，而Spraogue-Dawley大鼠90%的颅内体积扩张是在2个月龄时完成的。然后，计算未成熟大鼠硬脑膜所能产生的每日最大周向拉伸应变，并确定这两个月期间相应的硬脑膜每日双向拉伸应变。利用三参数单分子生长曲线，计算出出生(第0天)和60日龄大鼠硬脑膜每日最大等轴应力分别为9.7%和0.1%。由于未成熟的硬脑膜细胞可能承受高达约10%的拉伸应变，因此新生大鼠硬膜细胞在体外受到16%的等轴应变，并分析了硬膜细胞的增殖和基因表达谱。当暴露在机械应变下时，未成熟的硬脑膜细胞迅速增殖(24小时增殖细胞核抗原表达增加5.8倍)。此外，机械应变诱导硬脑膜细胞成骨细胞因子的产生明显上调，转化生长因子-β1信使RNA水平在3小时增加3.4倍，成纤维细胞生长因子-2蛋白水平在24小时增加4.5倍，48小时增加5.6倍。最后，机械应变增加了成骨细胞分化标志物硬脑膜细胞的表达(3小时时骨桥蛋白水平增加2.8倍)。这些结果表明，机械应变可以诱导硬脑膜生物学过程和基因表达的变化，这可能在协调新生儿颅骨的生长和愈合中发挥重要作用。
The human brain grows rapidly during the first 2 years of life. This growth generates tensile strain in the overlying dura mater and neurocranium. Interestingly, it is largely during this 2-year growth period that infants are able to reossify calvarial defects. This clinical observation is important because it suggests that calvarial healing is most robust during the period of active intracranial volume expansion. With a rat model, it was previously demonstrated that immature dura mater proliferates more rapidly and produces more osteogenic cytokines and markers of osteoblast differentiation than does mature dura mater. It was therefore hypothesized that mechanical strain generated by the growing brain induces immature dura mater proliferation and increases osteogenic cytokine expression necessary for growth and healing of the overlying calvaria. Human and rat (n = 40) intracranial volume expansion was calculated as a function of age. These calculations demonstrated that 83 percent of human intracranial volume expansion is complete by 2 years of age and 90 percent of Sprague-Dawley rat intracranial volume expansion is achieved by 2 months of age. Next, the maximal daily circumferential tensile strains that could be generated in immature rat dura mater were calculated, and the corresponding daily biaxial tensile strains in the dura mater during this 2-month period were determined. With the use of a three-Parameter monomolecular growth Curve, it was calculated that rat dura mater experiences daily equibiaxial strains of at most 9.7 percent and 0.1 percent at birth (day 0) and 60 days of age, respectively. Because it was noted that immature dural cells may experience tensile strains as high as approximately 10 percent, neonatal rat dural cells were Subjected to 16 percent equibiaxial strain in vitro, and dural cell proliferation and gene expression profiles were analyzed. When exposed to mechanical strain, immature dural cells rapidly proliferated (5.8-fold increase in proliferating cell nuclear antigen expression at 24 hours). Moreover, mechanical strain induced marked up-regulation of dural cell osteogenic cytokine production; transforming growth factor-beta1 messenger RNA levels increased 3.4-fold at 3 hours and fibroblast growth factor-2 protein levels increased 4.5-fold at 24 hours and 5.6-fold at 48 hours. Finally, mechanical strain increased dural cell expression of markers of osteoblast differentiation (2.8-fold increase in osteopontin levels at 3 hours). These findings suggest that mechanical strain can induce changes in dura mater biological processes and gene expression that may play important roles in coordinating the growth and healing of the neonatal calvaria.