Increased IGF-I and IGF-II mRNA and IGF-I peptide in fusing rat cranial sutures suggest evidence for a paracrine role of insulin-like growth factors in suture fusion
Increased IGF-I and IGF-II mRNA and IGF-I peptide in fusing rat cranial sutures suggest evidence for a paracrine role of insulin-like growth factors in suture fusion
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DOI：
10.1097/00006534-199907000-00019
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发表时间：
1999-07-01
影响因子：
3.6
通讯作者：
Longaker, MT
中科院分区：
文献类型：
--
作者：
Bradley, JP;Han, VKM;Longaker, MT
过早的颅缝融合，或颅缝融合，可能会导致颅面生长的粗大异常。颅缝融合的生物学基础仍然知之甚少。先前对Spraogue-Dawley大鼠额后缝的研究表明，颅缝下的区域硬脑膜指导着上面缝合的融合。为了探讨硬膜缝旁分泌信号在成骨分化和骨缝融合中的作用，作者研究了胰岛素样生长因子(IGF)I和IGF-II的可能作用。作者研究了IGF-I和IGF-II mRNA、IGF-I多肽和骨钙素(骨形态发生蛋白-4)蛋白在大鼠额后缝融合中的时空表达模式，并与开放的冠状缝合(对照)进行了比较。出生后80d(n=110)。用S-35标记的胰岛素样生长因子-I和胰岛素样生长因子-II反义核糖核酸探针进行原位杂交，分析额骨后缝和冠状缝合(专利、对照)中胰岛素样生长因子-I和胰岛素样生长因子-II的表达。通过计数每个细胞的放射自显影信号数量来量化IGF-I和IGF-II的mRNA水平。IGF-I和IGF-II在融合线下的硬脑膜细胞中均有表达，在融合开始前2~10天，IGF-I和IGF-II的相对mRNA丰度增加。在主动融合的第15天和第20天，在缝合结缔组织细胞中检测到IGF-I和IGF-II的mRNA。相反，在成骨前缘的大型成骨细胞中，IGF-I和IGF-II的mRNA表达很少。而IGF-I肽和骨钙素蛋白在15d(缝合融合期)的成骨细胞内呈强阳性反应。这些数据表明，硬脑膜来源的生长因子，如IGF-I和IGF-TI可能以旁分泌的方式传递硬脑膜-缝合的相互作用。这些多肽反过来刺激附近的成骨细胞产生骨促进生长因子，如骨钙素。
Premature cranial suture fusion, or craniosynostosis, can result in gross aberrations of craniofacial growth. The biology underlying cranial suture fusion remains poorly understood. Previous studies of the Sprague-Dawley rat posterior frontal suture, which fuses at between 12 and 20 days, have suggested that the regional dura mater beneath the cranial suture directs the overlying suture's fusion. To address the dura-suture paracrine signaling that results in osteogenic differentiation and suture fusion, the authors investigated the possible role of insulin-like growth factors (IGF) I and II. The authors studied the temporal and spatial patterns of the expression of IGF-I and IGF-II mRNA and IGF-I peptide and osteocalcin (bone morphogenetic protein-4) protein in fusing posterior frontal rat sutures, and they compared them with patent coronal (control) sutures.Ten Sprague-Dawley rats were studied at the following time points: 16, 18, and 20 days of gestation and 2, 5, 10, 15, 20, 30, 50, and 80 days after birth (n = 110). Posterior frontal and coronal (patent, control) sutures were analyzed for IGF-I and IGF-II mRNA expression by in situ hybridization by using S-35-labeled IGF-I and IGF-II antisense riboprobes. Levels of IGF-I and IGF-II mRNA were quantified by counting the number of autoradiograph signals per cell. IGF-I and osteocalcin immunoreactivity were identified by avidin-biotin peroxidase immunohistochemistry.IGF-I and IGF-II mRNA were expressed in dural, cells beneath fusing sutures, and the relative mRNA abundance increased between 2 and 10 days before initiation of fusion. Subsequently, IGF-I and IGF-II mRNA were detected in the suture connective tissue cells at 15 and 20 days during the time of active fusion. In contrast, within large osteoblasts of the osteogenic front, the expression of IGF-I and IGF-II mRNA was minimal. However, IGF-I peptide and osteocalcin protein were intensely immunoreactive within these osteoblasts at 15 days (during the period of suture fusion). These data suggest that the dura-suture interaction may be signaled in a paracrine fashion by dura-derived growth factors, such as IGF-I and IGF-TI. These peptides, in turn, stimulate nearby osteoblasts to produce bone-promoting growth factors, such as osteocalcin.