Liu J, Chanumolu S K, Krei Z, Albahrani M, Akhtam A, Jia Z, Wang X, Wang D, Otu H H, Reinhardt R A, Nawshad A
Department of Oral Biology College of Dentistry University of Nebraska Medical Center Lincoln NE USA.
Department of Electrical and Computer Engineering University of Nebraska-Lincoln Lincoln NE USA.
JBMR Plus. 2019 Jan 2;3(5):e10122. doi: 10.1002/jbm4.10122. eCollection 2019 May.
Local delivery of simvastatin (SIM) has exhibited potential in preventing inflammation and limiting bone loss associated with experimental periodontitis. The primary aim of this study was to analyze transcriptome changes that may contribute to SIM's reduction of periodontal inflammation and bone loss. We evaluate the global genetic profile and signaling mechanisms induced by SIM on experimental periodontitis bone loss and inflammation. Twenty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis around maxillary second molars (M2) either unilaterally (one side untreated, = 10) or bilaterally ( = 10). After the ligature removal at day 7, sites were injected with either carrier, pyrophosphate (PPi ×3), 1.5-mg SIM-dose equivalent SIM-pyrophosphate prodrug, or no injection. Three days after ligature removal, animals were euthanized; the M1-M2 interproximal was evaluated with μCT, histology, and protein expression. M2 palatal gingiva was harvested for RNA sequencing. Although ligature alone caused upregulation of proinflammatory and bone catabolic genes and proteins, seen in human periodontitis, SIM-PPi upregulated anti-inflammatory (IL-10, IL-1 receptor-like 1) and bone anabolic (insulin-like growth factor, osteocrin, fibroblast growth factor, and Wnt/ β-catenin) genes. The PPi carrier alone did not have these effects. Genetic profile and signaling mechanism data may help identify enhanced pharmacotherapeutic approaches to limit or regenerate periodontitis bone loss. © 2018 The Authors. Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
辛伐他汀（SIM）的局部递送在预防与实验性牙周炎相关的炎症和限制骨质流失方面已显示出潜力。本研究的主要目的是分析可能有助于SIM减少牙周炎症和骨质流失的转录组变化。我们评估了SIM对实验性牙周炎骨质流失和炎症诱导的整体基因谱和信号传导机制。将20只成年雌性Sprague Dawley大鼠单侧（一侧未处理，= 10）或双侧（= 10）在上颌第二磨牙（M2）周围进行结扎诱导实验性牙周炎。在第7天去除结扎线后，向位点注射载体、焦磷酸（PPi×3）、1.5mg SIM剂量等效的SIM - 焦磷酸前药，或不进行注射。去除结扎线三天后，对动物实施安乐死；用μCT、组织学和蛋白质表达评估M1 - M2邻间区域。采集M2腭侧牙龈用于RNA测序。尽管单独结扎会导致促炎和骨分解代谢基因及蛋白质上调，这在人类牙周炎中可见，但SIM - PPi上调了抗炎（IL - 10、IL - 1受体样1）和骨合成代谢（胰岛素样生长因子、骨分泌素、成纤维细胞生长因子和Wnt/β - 连环蛋白）基因。单独的PPi载体没有这些作用。基因谱和信号传导机制数据可能有助于确定增强的药物治疗方法以限制或再生牙周炎骨质流失。© 2018作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。
