In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force
In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force
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DOI：
10.1007/s00774-016-0737-z
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发表时间：
2017-01-01
影响因子：
3.3
通讯作者：
Takano-Yamamoto, Teruko
中科院分区：
文献类型：
--
作者：
Takeshita, Nobuo;Hasegawa, Masakazu;Takano-Yamamoto, Teruko
缝合线是连接颅面骨骼复合体中的骨的纤维组织。婴儿和青少年患者的颅颌面骨骼畸形可以通过对缝线施加张力以诱导缝骨形成来治疗。机械应力诱导的早期基因表达对长骨骨形成至关重要;然而，张力诱导的缝骨形成过程中的早期基因表达特征不明显。体内研究对于评价异质细胞群（如缝线）对机械应力的分子反应至关重要。在本文中，我们研究了在体内早期基因表达和潜在的调节机制，这种表达在张力施加颅缝，专注于血管化相关的基因。拉力在3小时内上调缝线中血管因子（例如血管内皮生长因子（Vegf）和内皮细胞标志物）的表达。结缔组织生长因子（Ctgf）和Rho相关的卷曲螺旋蛋白激酶2（Rock 2）的表达也上调张力。CTGF中和抗体和ROCK抑制剂Y-27632消除张力诱导的VEGF表达。此外，张力激活细胞外信号相关激酶1/2（ERK 1/2）信号在矢状缝，和ERK 1/2抑制剂，U 0126，部分抑制张力诱导的Ctgf表达。这些结果表明，张力诱导体内基因表达与血管化早期张力诱导缝骨形成。此外，VEGF基因表达的早期诱导受CTGF和ROCK 2调节。
Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes. Cranio- and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation. The early gene expression induced by mechanical stress is essential for bone formation in long bones; however, early gene expression during sutural bone formation induced by tensile force is poorly characterized. In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations, such as sutures. In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensile-force-applied cranial sutures, focusing on genes involved in vascularization. Tensile force upregulated expression of vascular factors, such as vascular endothelial growth factor (Vegf) and endothelial cell markers, in sutures within 3 h. The expression of connective tissue growth factor (Ctgf) and Rho-associated coiled-coil containing protein kinase 2 (Rock2) was also upregulated by tensile force. A CTGF-neutralizing antibody and the ROCK inhibitor, Y-27632, abolished tensile-force-induced Vegf expression. Moreover, tensile force activated extracellular signal-related kinase 1/2 (ERK1/2) signaling in sagittal sutures, and the ERK1/2 inhibitor, U0126, partially inhibited tensile-force-induced Ctgf expression. These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensile-force-induced sutural bone formation. Moreover, the early induction of Vegf gene expression is regulated by CTGF and ROCK2.