Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Center for Craniofacial Anomalies Research, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
J Dent Res. 2024 Jun;103(6):622-630. doi: 10.1177/00220345241242047. Epub 2024 May 7.
() targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of overexpression and inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration. Inhibition of using significantly increased osteogenic biomarkers of human embryonic palatal mesenchyme cells and promoted bone regeneration in rat tooth socket defects. In rat maxillary M1 molar extractions, the supporting tooth structures were removed with an implant drill to yield a 3-mm defect in the alveolar bone. A collagen sponge was inserted into the open alveolar defect and plasmid DNA was added to the sponge and the wound sutured to protect the sponge and close the defect. It was important to remove the existing tooth supporting structure, which can influence alveolar bone regeneration. The alveolar bone was regenerated in 4 wk. The collagen sponge acts to stabilize and deliver the DNA to cells entering the sponge in the bone defect. We show that mesenchymal stem cells expressing CD90 and Stro-1 enter the sponges, take up the DNA, and express initiates a bone regeneration program in transformed cells in vivo. In vitro inhibition of was found to upregulate Wnt and BMP signaling activity as well as , and associated with osteogenesis. Liver and blood toxicity testing of -treated rats showed no increase in several biomarkers of liver disease. These results demonstrate the therapeutic function of for rapid bone regeneration. Furthermore, the studies were designed to demonstrate the ease of use of in solution and applied using a syringe in the clinic through a simple one-time application.
() 靶向多个参与成骨分化和骨发育的信号通路。然而，其在成骨和骨再生中的治疗功能尚不清楚。在这项研究中，我们使用体外和体内模型，通过基于质粒的 miR 抑制剂系统（PMIS），研究了 过表达和抑制对成骨分化和骨再生的分子功能。使用 抑制 显著增加了人胚胎腭中胚层细胞的成骨生物标志物，并促进了大鼠牙槽骨缺损的骨再生。在大鼠上颌 M1 磨牙拔除术中，用种植体钻头去除支持牙齿结构，在牙槽骨中产生 3mm 缺损。将胶原海绵插入开放的牙槽骨缺损中，并向海绵中添加 质粒 DNA 并缝合伤口以保护海绵并封闭缺损。去除现有的牙齿支撑结构很重要，因为这会影响牙槽骨再生。4 周后牙槽骨再生。胶原海绵的作用是稳定并将 DNA 递送至进入骨缺损海绵中的细胞。我们表明，表达 CD90 和 Stro-1 的间充质干细胞进入海绵，摄取 DNA，并表达 启动体内转化细胞的骨再生程序。体外抑制 发现上调 Wnt 和 BMP 信号活性以及与成骨相关的 。用 处理的大鼠的肝和血液毒性检测显示，几种肝病生物标志物没有增加。这些结果表明 对快速骨再生具有治疗作用。此外，这些研究旨在证明 在溶液中的易用性，并通过在诊所中使用注射器进行简单的一次性应用来应用。
