Orthodontic tensile strain induces angiogenesis via type IV collagen degradation by matrix metalloproteinase-12
Orthodontic tensile strain induces angiogenesis via type IV collagen degradation by matrix metalloproteinase-12
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DOI：
10.1111/jre.12453
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发表时间：
2017-10-01
影响因子：
3.5
通讯作者：
Nakamura, Y.
中科院分区：
文献类型：
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作者：
Narimiya, T.;Wada, S.;Nakamura, Y.
背景与目的正畸牙齿移动过程中，牙周韧带(PDL)发生动态改建，需要足够的血液供应才能再生。然而，对OTM过程中血管的重塑知之甚少。在本研究中，我们假设正畸张应力在OTM早期通过降解血管内皮细胞基底膜中的IV型胶原(Col-IV)而上调张力区基质金属蛋白酶-12(MMP12)的表达，并诱导血管生成。材料与方法应用免疫组织化学方法检测OTM早期大鼠PDL张力区的时空表达。对体外培养的人永生化PDL细胞系(HPL细胞)施加连续拉伸应变，检测基质金属蛋白酶-12(MMP12)的表达。免疫组织化学方法检测MMP12和Col-IV在体内的共定位。为了研究HPL细胞产生的基质金属蛋白酶-12(MMP12)是否能降解Col-IV，将重组Col-IV与HPL细胞培养上清液孵育。用免疫印迹法检测体外培养的完整Col-IV。结果正畸张应力在体内和体外均可诱导PDL细胞表达基质金属蛋白酶-12。免疫组织化学结果显示，在PDL张力区与Col-IV阳性的小管区相邻可见MMP12阳性细胞。HPL细胞培养上清液中的MMP12可降解重组Col-IV，特异性的MMP12抑制剂可阻断Col-IV的降解。显微计算机断层扫描和常规组织学分析显示，OTM后PDL张力区血管面积增加。结论正畸张力可上调PDL张力区基质金属蛋白酶-12的表达，并通过降解血管内皮细胞基底膜中的Col-IV而诱导血管生成。
Background and ObjectiveDuring orthodontic tooth movement (OTM), periodontal ligament (PDL) is remodeled dynamically, which requires sufficient blood supply for the regeneration of PDL. However, little is known about the remodeling of blood vessels during OTM. In this study, we hypothesized that the orthodontic tensile strain upregulates matrix metalloproteinase-12 (MMP-12) expression in the tension zone and induces angiogenesis via degradation of type IV collagen (Col-IV) in vascular endothelial basement membrane during the early stage of OTM.Material and MethodsTemporal and spatial MMP-12 expression in the tension zone of PDL, during the early stage of OTM, were examined by immunohistochemistry in rats. Continuous tensile strain was applied to cultured human immortalized PDL cell lines (HPL cells) and MMP-12 expression was examined in vitro. Colocalization of MMP-12 and Col-IV in vivo were examined by immunohistochemistry. To investigate whether MMP-12 produced by HPL cells could degrade Col-IV, recombinant Col-IV was incubated in the culture supernatants of HPL cells. Intact Col-IV in vitro was also examined by western blot analysis. Finally, the changes in blood vessels in the PDL were examined by micro-computed tomography analysis with perfused contrast agents and by conventional histological analysis.ResultsOrthodontic tensile strain induced MMP-12 expression in PDL cells in vivo and in vitro. Immunohistochemistry revealed that MMP-12-positive cells were observed adjacent to the Col-IV-positive tubular area in the tension zone of PDL. MMP-12 in culture supernatant of HPL cells degraded recombinant Col-IV, and specific MMP-12 inhibitor blocked the Col-IV degradation. Micro-computed tomography analysis and conventional histological analysis demonstrated that the areas of blood vessels were increased in the tension zone of the PDL after OTM.ConclusionWe discovered that the orthodontic tensile strain upregulates MMP-12 expression in the tension zone of PDL and induces angiogenesis via degradation of Col-IV in the vascular endothelial basement membrane.