抑制miR-203-3p表达对糖尿病小鼠牙种植体周围骨形成的影响  

Effect of inhibiting miR-203-3p expression on bone formation around dental implants in diabetic mice

作　　者：李孔梅 罗诒财 李昊[1] Li Kongmei;Luo Yicai;Li Hao(Department of Prosthodontics,College of Stomatology,Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西医科大学口腔医学院口腔修复科,广西壮族自治区南宁市530021

出　　处：《中国组织工程研究》2022年第32期5102-5106,共5页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(82060195,81600833),项目负责人:李昊。

摘　　要：背景:糖尿病状态下牙种植体周围骨形成不佳,机制不明确。近年研究表明,miR-203-3p可调节多种疾病状态下的骨形成,在糖尿病颌骨组织中高表达,然而是否对牙种植体周围骨形成也有影响,尚不清楚。目的:探讨抑制miR-203-3p表达对糖尿病小鼠牙种植体周围骨形成的影响。方法:C57BL/6J小鼠48只,随机取血糖正常小鼠12只作为正常组,其余小鼠构建糖尿病模型后,随机分为糖尿病组、糖尿病+antago miR-NC组、糖尿病+antagomiR-203-3p组,每组12只。所有小鼠构建左侧上颌牙种植模型,糖尿病+antagomiR-NC组注射阴性对照antago miR-NC(0.25 mmol/L),糖尿病+antago miR-203-3p组注射antago miR-203-3p(0.25 mmol/L),其余两组注射等体积生理盐水。3个月后取小鼠左侧上颌骨组织,Micro-CT、苏木精-伊红染色观察种植体周围骨形成情况;qRT-PCR检测种植体周围骨组织中miR-203-3p、Smad1、碱性磷酸酶、Runx2、Osterix、Ⅰ型胶原基因表达。结果与结论:①Micro-CT检测显示,与糖尿病组、糖尿病+antago miR-NC组比较,糖尿病+antago miR-203-3p组种植体周围牙槽骨组织形成情况较好,骨体积分数、骨小梁厚度较高(P <0.05);②苏木精-伊红染色显示,糖尿病+antago miR-203-3p组种植体周围骨形成Lane-Sandhu评分高于糖尿病组、糖尿病+antago miR-NC组(P <0.05);③qRT-PCR结果显示,糖尿病+antago miR-203-3p组种植体周围骨组织miR-203-3p基因表达水平低于糖尿病组、糖尿病+antago miR-NC组(P <0.05),Smad1、碱性磷酸酶、Runx2、Osterix、Ⅰ型胶原基因表达水平高于糖尿病组、糖尿病+antago miR-NC组(P <0.05);④结果表明,在高糖状态下,抑制miR-203-3p表达有利于种植体周围骨形成,这些作用可能与调节Smad信号通路及碱性磷酸酶、Runx2、Osterix、Ⅰ型胶原等成骨相关因子表达有关。BACKGROUND:Up to now,dental implant has become an important restoration for patients with tooth loss,and bone formation around dental implants is the key to the success of dental implantation.There is often a poor bone formation around dental implants under diabetic conditions and the mechanism remains unclear.Recent studies have shown that miR-203-3p regulates bone formation in different diseases,and strongly expressed in jaw bone tissues under diabetic conditions.However,it is unclear whether miR-203-3p can influence bone formation around dental implants.OBJECTIVE:To investigate the effect of inhibiting miR-203-3p expression on bone formation around dental implants in diabetic mice.METHODS:Twelve mice with normal blood glucose we re randomly selected as normal group from forty-eight C57BL/6J mice.The other 36 mice were selected to make diabetic models and then randomly divided into diabetic group,diabetes+antago miR-NC group,and diabetes+antago miR-203-3p group(n=12 per gro up).Single implant was inserted into the left maxilla of each mouse.Diabetic+antago miR-NC group was injected with antago miR-203-3p negative control,antago miR-NC(0.25 mmol/L).Diabetes+antago miR-203-3p group was injected with antago miR-203-3p(0.25 mmol/L).The other two diabetic groups were injected with the equal volume of normal saline.After 3 months,the left maxillary bone tissue of mice was collected,and the bone formation around dental implants was detected using micro-CT and hematoxylin-eosin staining.qRT-PCR was used to detect the gene expression of miR-203-3p,Smad1,alkaline phosphatase,Runx2,Oste rix,and type I collagen in bone tissue around dental implants.RESULTS AND CONCLUSION:Micro-CT results showed that compared with the diabetic group and diabetes+antago miR-NC group,the diabetes+antago miR-203-3p group showed better alveolar bone formation around dental implants and higher bone volume fraction and bone trabecular thickness(P <0.05).Hematoxylin-eosin staining results showed that the Lane-Sandhu sco re of bone formation around

关 键 词：糖尿病 miR-203-3p 种植体 骨形成 小鼠 SMAD1 RUNX2 OSTERIX 碱性磷酸酶 Ⅰ型胶原 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学]