Immature versus mature dura mater: II. Differential expression of genes important to calvarial reossification

Immature versus mature dura mater: II. Differential expression of genes important to calvarial reossification
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DOI:
10.1097/00006534-200009030-00016
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发表时间:
2000-09-01
影响因子:
3.6
通讯作者:
Longaker, MT
Longaker, MT
中科院分区:
医学1区
文献类型:
--
作者:
Greenwald, JA;Mehrara, BJ;Longaker, MT

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未成熟动物和新生儿协调成功颅骨再骨化的能力得到了很好的描述。这种能力在成熟动物和2岁以上的人类中明显减弱。先前的研究表明硬脑膜是成功颅骨再骨化的关键。作者以前曾报道过未成熟但不成熟的硬脑膜组织能够形成成骨生长因子和细胞外基质分子的高表达。这些发现导致了一种假设,即未成熟和成熟硬脑膜组织中成骨生长因子和细胞外基质分子的差异表达可能是临床观察到的表型的原因(即,未成熟的动物会使颅骨缺损再骨化,而成熟的动物则不会)。本研究通过分析转化生长因子(TGF)- β 3、III型胶原和碱性磷酸酶mRNA的表达,继续探索这一假说。从新鲜收获的未成熟硬脑膜组织(n = 60)和成熟硬脑膜组织(n = 10)中分离的总RNA进行Northern blot分析显示,与成熟硬脑膜组织相比,未成熟硬脑膜组织中TGF-PS、III型胶原和碱性磷酸酶mRNA的表达分别增加了3倍、18倍和9倍。此外,对未成熟(n = 60)和成熟硬脑膜(n = 10)的硬脑膜细胞培养物进行碱性磷酸酶活性染色,以确定成骨样细胞的存在。未成熟硬脑膜细胞碱性磷酸酶染色显示碱性磷酸酶阳性细胞数量明显高于成熟硬脑膜组织(p < 0.001)。除了提供成骨体液因子(即生长因子和细胞外基质分子)外,这一发现表明,未成熟但未成熟的硬脑膜可能提供细胞因子(即成骨细胞),从而增强成功的颅骨再骨化。这些研究支持了一个假设,即未成熟而非成熟的硬脑膜组织对成骨生长因子(如tgf - β 3)和细胞外基质分子(如III型胶原和碱性磷酸酶)的精细加工可能对成功的颅骨再骨化至关重要。此外,这些研究首次表明,未成熟的硬脑膜组织可能提供细胞成分(即成骨细胞)来增强这一过程。
The ability of immature animals and newborns to orchestrate successful calvarial reossification is well described. This capacity is markedly attenuated in mature animals and in humans greater than 2 years of age. Previous studies have implicated the dura mater as critical to successful calvarial reossification. The authors have previously reported that immature, but not mature, dural tissues are capable of elaborating a high expression of osteogenic growth factors and extracellular matrix molecules. These findings led to the hypothesis that a differential expression of osteogenic growth factors and extracellular matrix molecules by immature and mature dural tissues may be responsible for the clinically observed phenotypes (i.e., immature animals reossify calvarial defects; mature animals do not). This study continues to explore the hypothesis through an analysis of transforming growth factor (TGF)-beta 3, collagen type III, and alkaline phosphatase mRNA expression.Northern blot analysis of total RNA isolated from freshly harvested immature (n = 60) and mature (n = 10) dural tissues demonstrated a greater than three-fold, 18-fold, and nine-fold increase in TGF-PS, collagen type III, and alkaline phosphatase mRNA expression, respectively, in immature dural tissues as compared with mature dural tissues. Additionally, dural cell cultures derived from immature (n = 60) and mature dura mater ( n = 10) were stained for alkaline phosphatase activity to identify the presence of osteoblast-like cells. Alkaline phosphatase staining of immature dural cells revealed a significant increase in the number of alkaline phosphatase-positive cells as compared with mature dural tissues (p < 0.001). In addition to providing osteogenic humoral factors (i.e., growth factors and extracellular matrix molecules), this finding suggests that immature, but not mature, dura mater may provide cellular elements (i.e., osteoblasts) that augment successful calvarial reossification.These studies support the hypothesis that elaboration of osteogenic growth factors (i.e., TGF-beta 3) and extracellular matrix molecules (i.e., collagen type III and alkaline phosphatase) by immature, but not mature, dural tissues may be critical for successful calvarial reossification. In addition, these studies suggest for the first time that immature dural tissues may protide cellular elements (i.e., osteoblasts) to augment this process.