Behm Christian, Nemec Michael, Blufstein Alice, Schubert Maria, Rausch-Fan Xiaohui, Andrukhov Oleh, Jonke Erwin
Division of Orthodontics, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.
Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, 1090 Vienna, Austria.
Int J Mol Sci. 2021 Jan 20;22(3):1027. doi: 10.3390/ijms22031027.
The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and gene expression. IL-1β-induced gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.
牙周韧带（PDL）通过细胞外基质（ECM）重塑对正畸力作出反应，在此过程中，人牙周韧带来源的间充质基质细胞（hPDL-MSCs）通过产生基质金属蛋白酶（MMPs）及其局部抑制剂（TIMPs）而在很大程度上参与其中。除正畸力外，MMPs和TIMPs的合成还受正畸治疗期间发生的无菌性炎症影响。白细胞介素（IL）-1β是这一过程中最丰富的炎症介质之一，在周期性低强度正畸拉伸力存在的情况下，它对MMPs和TIMPs的表达有至关重要的影响。在本研究中，我们首次旨在探究IL-1β如何诱导MMPs、TIMPs的表达，以及在体外以静态施加模式施加低强度正畸拉伸应变后，hPDL-MSCs中IL-1β是如何变化的。因此，用IL-1β联合6%伸长率的静态拉伸应变（STS）刺激原代hPDL-MSCs。6小时和24小时后，检测MMP-1、MMP-2、TIMP-1和IL-1β的表达水平。单独的STS对所研究靶基因的基础表达没有影响，而IL-1β导致这些基因的表达增加。二者共同作用时，24小时后它们增加了MMP-1的基因和蛋白表达以及[此处原文缺失相关基因名称]的基因表达。6小时后，STS降低了IL-1β诱导的MMP-1合成及[此处原文缺失相关基因名称]的基因表达。6小时和24小时后，STS均降低了IL-1β诱导的[此处原文缺失相关基因名称]的基因表达。在两个时间点，IL-1β诱导的[此处原文缺失相关基因名称]的基因表达均增加。此外，本研究表明胎牛血清（FBS）总体上抑制了IL-1β诱导的MMP-1、MMP-2和TIMP-1的表达。此外，它使STS对IL-1β诱导表达产生较低或相反的影响。这些观察结果表明，在使用静态施加形式时，低强度正畸拉伸应变可能有利于hPDL-MSCs产生更具炎症性和破坏性的反应，并且这种反应在体外受到FBS存在的高度影响。
