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纳米颗粒介导的 PPARγ 基因递送至牙种植体通过糖尿病大鼠模型中线粒体生物发生改善骨整合。

Nanoparticle mediated PPARγ gene delivery on dental implants improves osseointegration via mitochondrial biogenesis in diabetes mellitus rat model.

机构信息

Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.

Department of Dental Materials, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.

出版信息

Nanomedicine. 2017 Jul;13(5):1821-1832. doi: 10.1016/j.nano.2017.02.020. Epub 2017 Mar 8.

Abstract

Diabetes mellitus (DM) has a detrimental effect on osseointegration, stability and longevity of implants due to osteoporosis. In this study, PPARγ-loaded dental implants were investigated for the improvement of osseointegration and peri-implantitis. Chitosan gold nanoparticles conjugated with PPARγ cDNA were introduced on titanium mini-implant surfaces for PPARγ release to rat mandibular. DM-induced rat mandible showed structural changes such as decreased bone mass and increased inflammatory molecules, and diminution of PPARγ expression and bone formation molecules compared to normal rats. PPARγ induced bone formation via reduction of inflammatory molecules even under glucose oxidative stress. Furthermore, PPARγ strongly activated mitochondrial biogenesis and cell viability via p-AMK and Wnt/β-catenin signaling. Consequently, PPARγ gene delivery on regional dental implants contributed osseointegration, new bone formation and mineralization in DM-induced rats. This study demonstrates that PPARγ can be used as a therapeutic gene with dental implantation in diabetic patients since regional PPARγ expression enhances osseointegration and implant longevity.

摘要

糖尿病(DM)可导致骨质疏松症,从而对种植体的骨整合、稳定性和寿命产生不利影响。在这项研究中,研究了载 PPARγ 的牙科种植体,以改善骨整合和种植体周围炎。将与 PPARγ cDNA 缀合的壳聚糖金纳米颗粒引入钛微型种植体表面,以释放 PPARγ 到大鼠下颌骨。与正常大鼠相比,DM 诱导的大鼠下颌骨表现出结构变化,如骨量减少和炎症分子增加,以及 PPARγ 表达和骨形成分子减少。PPARγ 通过降低炎症分子甚至在葡萄糖氧化应激下诱导骨形成。此外,PPARγ 通过 p-AMK 和 Wnt/β-catenin 信号强烈激活线粒体生物发生和细胞活力。因此,在 DM 诱导的大鼠中,局部牙科种植体上的 PPARγ 基因传递有助于骨整合、新骨形成和矿化。本研究表明,PPARγ 可与牙种植一起作为一种治疗基因用于糖尿病患者,因为局部 PPARγ 表达可增强骨整合和种植体的寿命。

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