Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1
Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1
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DOI：
10.1359/jbmr.051216
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发表时间：
2006-04-01
影响因子：
6.2
通讯作者：
Matsuo, K
中科院分区：
文献类型：
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作者：
Nishiwaki, T;Yamaguchi, T;Matsuo, K
FRA1转基因(TG)小鼠出现骨硬化并表现出骨基质蛋白表达的改变。我们发现在Fra1TG成骨细胞中Thbs1和Tltbs2的表达减少。Fra1TG和非骨硬化性Thbs1(-/-)Thbs2(-/-)小鼠共享边缘到边缘咬合。因此，血栓反应蛋白的表达减少可能是颅面部畸形的独立于骨硬化症的原因。简介：过度表达转录因子激活蛋白-1(AP-1)的一种成分Fra1.的TG小鼠表现为由成骨细胞的细胞自主异常引起的进行性骨硬化。材料和方法：在成骨细胞培养中，通过茜素红染色、定量RT-PCR和Western blotting检测Fra1过表达引起的骨基质产生的改变。通过骨组织形态计量学检查卵巢切除的反应性。结果：在体外分化的Fra1TG成骨细胞和Fra1TG小鼠骨中，凝血酶敏感蛋白-1(Thbs1)和凝血酶敏感蛋白-2(Thbs2)的表达均降低。尽管骨基质蛋白发生了变化，但卵巢切除会导致FRA1TG小鼠与野生型小鼠一样的高周转性骨丢失。FRA1TG小鼠和Thbs1(-/-)Thbs2(-/-)小鼠没有表现出骨硬化，表现出与颅面畸形相关的边到边咬合表型。结论：这些数据表明FRA1中血栓反应蛋白的表达减少。TG小鼠是颅面畸形的基础，与骨硬化无关。
Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Tltbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1(-/-)Thbs2(-/-) mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis.Introduction: Tg mice overexpressing Fra1., a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 To osteoblasts.Materials and Methods: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT.Results: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1(-/-) Thbs2(-/-) mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism.Conclusions: These data suggest that reduced expression of thrombospondins in Fra1. Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.