Dura mater biology: Autocrine and paracrine effects of fibroblast growth factor 2
Dura mater biology: Autocrine and paracrine effects of fibroblast growth factor 2
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DOI：
10.1097/00006534-200202000-00035
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发表时间：
2002-02-01
影响因子：
3.6
通讯作者：
Longaker, MT
中科院分区：
文献类型：
--
作者：
Spector, JA;Greenwald, JA;Longaker, MT
硬脑膜，脑膜的最外层，被认为是必不可少的颅骨形态发生，产后缝融合，颅骨缺损的骨修复。尽管许多研究表明硬脑膜的基本作用，有很少的信息自分泌和旁分泌机制调节硬脑膜细胞生物学在颅骨骨化。在作者实验室进行的先前工作表明，来自6日龄幼鼠的非缝合相关硬脑膜细胞表达高水平的成纤维细胞生长因子2（FGF-2），而来自60日龄成年大鼠的硬脑膜细胞表达很少的FGF-2。由于年轻的哺乳动物可以成功地治愈大的颅骨缺损，作者试图研究FGF-2对硬脑膜细胞增殖，基因表达和碱性磷酸酶产生的自分泌和/或旁分泌作用。从6日龄Sprague-Dawley大鼠幼仔建立非缝线相关硬脑膜细胞培养物，然后用重组人FGF-2（rhFGF-2; 10 ng/ml）刺激。rhFGF-2刺激的硬脑膜细胞在24小时的增殖速度明显快于未处理的硬脑膜细胞（2.1 x 10（-5）+/- 3.2 x 10（4）对比1.1 x 10（5）+/- 1.8 x 10（4），小于或等于0.001）和48小时（2.3 x 10（5）+/- 4.2 x 10（4）vs 1.2 x 10（5）+/- 1.3 x 10（4），小于或等于0.001）。此外，用rhFGF-2刺激的硬脑膜细胞表达的增殖细胞核抗原是对照培养物的7倍。用rhFGF-2治疗增加了硬脑膜细胞对骨骼修复重要基因的表达：FGF-2（7倍），转化生长因子β 1（3倍），转化生长因子β 3（4倍）和I型胶原（4倍）。此外，rhFGF-2增加硬脑膜细胞骨桥蛋白的表达（2倍），骨桥蛋白是成骨细胞分化的“晚期”标志物。有趣的是，与对照培养物相比，rhFGF-2处理24小时后，硬脑膜细胞碱性磷酸酶活性（成骨细胞分化的“早期”标志物）显著降低（0.005+/-0.001与0.01+/-0.003，小于或等于0.01）和48小时（0.004+/-0.0009与0.01+/-0.0009）。总之，这些数据提供了深入了解FGF-2对硬脑膜生物学的自分泌和旁分泌作用。
The dura mater, the outermost layer of the meninges, is thought to be essential for calvarial morphogenesis, postnatal suture fusion, and osseous repair of calvarial defects. Despite numerous studies illustrating the fundamental role of the dura mater, there is little information about the autocrine and paracrine mechanisms regulating dural cell biology during calvarial ossification. Previous work conducted in the authors' laboratory demonstrated that non-suture-associated dural cells from 6-day-old rat pups expressed high levels of fibroblast growth factor 2 (FGF-2), whereas dural cells from 60-day-old adult rats expressed very little FGF-2. Because young mammals can successfully heal large calvarial defects, the authors sought to investigate the autocrine and/or paracrine effects of FGF-2 on the proliferation, gene expression, and alkaline phosphatase production of dural cells. Cultures of non-suture-associated dural cells were established from 6-day-old Sprague-Dawley rat pups and then stimulated with recombinant human FGF-2 (rhFGF-2; 10 ng/ml). Dural cells stimulated with rhFGF-2 proliferated significantly faster than untreated dural cells at 24 hours (2.1 x 10(-5) +/- 3.2 x 10(4) Versus 1.1 x 10(5) +/- 1.8 x 10(4), pless than or equal to0.001) and 48 hours (2.3 x 10(5) +/- 4.2 x 10(4) versus 1.2 x 10(5) +/- 1.3 x 10(4), pless than or equal to0.001). Moreover, dural cells stimulated with rhFGF-2 expressed 7-fold more proliferating cell nuclear antigen than did control cultures. Treatment with rhFGF-2 increased dural cell expression of genes important for skeletal repair: FGF-2 (7-fold), transforming growth factor beta1 (3-fold), transforming growth factor beta3 (4-fold), and type I collagen (4-fold). Further, p more, rhFGF-2 increased dural cell expression of osteopontin (2-fold), a "late" marker of osteoblastic differentiation. Interestingly, dural cell alkaline phosphatase activity, an "earlier" marker of osteoblast differentiation, was significantly decreased by treatment with rhFGF-2 compared with control cultures at 24 hours (0.005+/-0.001 versus 0.01+/-0.003, pless than or equal to0.01) and 48 hours (0.004+/-0.0009 versus 0.01+/-0.0009). Together these data provide insight into the autocrine and paracrine effects of FGF-2 on the biology of the dura mater.