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基于间充质干细胞沉默信息调节因子 7 蛋白分析改善大鼠胫骨缺损的修复机制和 miRNA 表达谱。

Improving the repair mechanism and miRNA expression profile of tibial defect in rats based on silent information regulator 7 protein analysis of mesenchymal stem cells.

机构信息

Orthopaedic Trauma, Maoming People's Hospital, Maoming City, China.

出版信息

Bioengineered. 2022 Mar;13(3):4674-4687. doi: 10.1080/21655979.2022.2027066.

DOI:10.1080/21655979.2022.2027066
PMID:35139764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973621/
Abstract

The aim of this study was to verify the role of Silent Information Regulator 7 (SIRT7) in improving the repair mechanism of bone marrow mesenchymal stem cells (BMMSCs) and the expression of microribonucleic acid (miRNA). Human BMMSCs were extracted from patients with femoral fractures, and the proliferation activity of human BMMSCs before and after knockout SIRT7 and the expression levels of bone-related genes and proteins were compared. Thirty-two 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a blank group, a chitosan scaffold group, a control group, and a silence information regulator knockout group 7 (n = 8). In addition to the blank group, the chitosan scaffold, the green fluorescent protein (GFP) transfected stem cell composite chitosan scaffold, and the SIRT7 knockout stem cell composite chitosan scaffold were implanted in the other three groups, respectively. The X-rays and small animal in vivo three-dimensional tomography (Micro-CT) were adopted to quantitatively analyze the volume fraction, the number of trabeculae, and the connection density. Compared with the other three groups, the bone defect was formed more in the medullary mesenchymal stem cell knockout group, and the bone volume fraction, number of trabeculae and connection density were significantly increased ( < 0.05). MiR-98-5p can significantly promote the formation of bone molecules and bone structure in rats ( < 0.05). Human BMMSCs combined with chitosan scaffold can accelerate the repair of tibial defects. MiR-98-5p targeting and regulating bone formation gene (CKIP-1) could significantly improve the process of osteogenesis in rats.

摘要

本研究旨在验证沉默信息调节因子 7(SIRT7)在改善骨髓间充质干细胞(BMMSCs)修复机制和微小 RNA(miRNA)表达中的作用。从股骨骨折患者中提取人 BMMSCs,比较敲除 SIRT7 前后人 BMMSCs 的增殖活性以及骨相关基因和蛋白的表达水平。将 32 只 8 周龄雄性 Sprague-Dawley(SD)大鼠随机分为空白组、壳聚糖支架组、对照组和沉默信息调节因子敲除 7 组(n=8)。除空白组外,壳聚糖支架、绿色荧光蛋白(GFP)转染干细胞复合壳聚糖支架和 SIRT7 敲除干细胞复合壳聚糖支架分别植入其他三组。采用 X 射线和小动物体内三维断层扫描(Micro-CT)定量分析体积分数、小梁数和连接密度。与其他三组相比,骨髓间充质干细胞敲除组骨缺损形成较多,骨体积分数、小梁数和连接密度均显著增加(<0.05)。miR-98-5p 可显著促进大鼠骨分子和骨结构的形成(<0.05)。人 BMMSCs 与壳聚糖支架结合可加速胫骨缺损的修复。miR-98-5p 靶向并调节骨形成基因(CKIP-1)可显著改善大鼠成骨过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/472f4c1d4e03/KBIE_A_2027066_F0010_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/44b78c6e4a3a/KBIE_A_2027066_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/41521dbd8b41/KBIE_A_2027066_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/8b98c0eb9196/KBIE_A_2027066_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/472f4c1d4e03/KBIE_A_2027066_F0010_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/4ce3728ee1cc/KBIE_A_2027066_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/f5269446445c/KBIE_A_2027066_F0003_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/b65d2f5fa039/KBIE_A_2027066_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/624d46eac4b0/KBIE_A_2027066_F0006_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/44b78c6e4a3a/KBIE_A_2027066_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/41521dbd8b41/KBIE_A_2027066_F0008_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/8b98c0eb9196/KBIE_A_2027066_F0009_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b650/8973621/472f4c1d4e03/KBIE_A_2027066_F0010_OC.jpg

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