Dihydrotestosterone stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells and induces cranial suture fusion
Dihydrotestosterone stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells and induces cranial suture fusion
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DOI：
10.1097/01.prs.0000279527.99734.bf
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发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Kirschner, Richard E.
中科院分区：
文献类型：
--
作者：
Lin, Ines C.;Slemp, Alison E.;Kirschner, Richard E.
背景：男婴中同位缝和矢状缝缝早闭的发生率较高，表明雄激素在早期颅面发育中的作用。这些实验表征了雄激素刺激对胎儿硬脑膜和颅骨骨细胞的生长和分化以及颅缝融合的影响。方法：分离并培养原代小鼠胎儿（E18）硬脑膜细胞和颅骨成骨细胞。用 5α-二氢睾酮（0 至 1000 nM）处理细胞 48 小时。通过非放射性增殖测定检查细胞增殖；通过逆转录酶聚合酶链反应测定碱性磷酸酶、转化生长因子（TGF）-β1、骨基质蛋白骨桥蛋白、骨钙素和I型胶原的mRNA表达。在单独的实验中，完整的胎儿颅骨在含有 10 nM 5 α-二氢睾酮的组织培养物中生长 7 和 14 天，然后进行组织学检查。结果：5 nM 雄激素刺激使胎儿硬脑膜细胞增殖增加 46.0%，胎儿颅骨成骨细胞增殖增加 20.5%。 5α-二氢睾酮可增强骨桥蛋白、骨钙素和 I 型胶原的硬脑膜表达，TGF-β1 和碱性磷酸酶的表达也增强。雄激素刺激增加了颅骨成骨细胞碱性磷酸酶和TGF-β1的表达，但引起骨钙素、骨桥蛋白和I型胶原蛋白表达的微小变化。在组织培养中，5a-二氢睾酮刺激类骨形成和矢状缝融合。结论：雄激素刺激硬脑膜细胞和胎儿颅盖分离的成骨细胞可促进细胞增殖和成骨细胞分化，并可诱导颅缝融合。这些结果表明，性类固醇激素信号传导可能通过硬脑膜细胞的骨分化刺激骨缝成骨，从而解释了非综合征性颅缝早闭的男性患病率。
Background: The higher prevalence of metopic and sagittal suture synostosis in male infants suggests a role for androgens in early craniofacial development. These experiments characterize the influence of androgen stimulation on growth and differentiation of fetal dural and calvarial bone cells and on cranial suture fusion.Methods: Primary murine fetal (E18) dural cells and calvarial osteoblasts were isolated and cultured. Cells were treated for 48 hours with 5 alpha-dihydrotestosterone (0 to 1000 nM). Cell proliferation was examined by nonradioactive proliferation assay; mRNA expression of alkaline phosphatase, transforming growth factor (TGF)-beta 1, and the bone matrix proteins osteopontin, osteocalcin, and type I collagen was determined by reverse-transcriptase polymerase chain reaction. In separate experiments, intact fetal calvariae were grown in tissue culture with 10 nM 5 alpha-dihydrotestosterone for 7 and 14 days and then examined histologically.Results: Androgen stimulation at 5 nM increased proliferation of fetal dural cells by 46.0 percent and of fetal calvarial osteoblasts by 20.5 percent. Dural expression of osteopontin, osteocalcin, and type I collagen was enhanced by 5 alpha-dihydrotestosterone, as was that of TGF-beta 1 and alkaline phosphatase. Androgen stimulation increased calvarial osteoblast expression of alkaline phosphatase and TGF-beta 1 but induced little change in expression of osteocalcin, osteopontin, and type I collagen. In tissue culture, 5a-dihydrotestosterone stimulated osteoid formation and fusion of sagittal sutures.Conclusions: Androgen stimulation of dural cells and osteoblasts isolated from fetal calvaria promotes cell proliferation and ostcoblastic differentiation and can induce cranial suture fusion. These results suggest that sex steroid hormone signaling may stimulate sutural osteogenesis by means of osteodifferentiation of dural cells, thus explaining the male prevalence of nonsyndromic craniosynostosis.