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Runx2修饰的脂肪来源干细胞促进前交叉韧带重建中肌腱移植物的整合。

Runx2-Modified Adipose-Derived Stem Cells Promote Tendon Graft Integration in Anterior Cruciate Ligament Reconstruction.

作者信息

Zhang Xin, Ma Yong, Fu Xin, Liu Qiang, Shao Zhenxing, Dai Linghui, Pi Yanbin, Hu Xiaoqing, Zhang Jiying, Duan Xiaoning, Chen Wenqing, Chen Ping, Zhou Chunyan, Ao Yingfang

机构信息

Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China.

Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing, China.

出版信息

Sci Rep. 2016 Jan 8;6:19073. doi: 10.1038/srep19073.

DOI:10.1038/srep19073
PMID:26743583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4705474/
Abstract

Runx2 is a powerful osteo-inductive factor and adipose-derived stem cells (ADSCs) are multipotent. However, it is unknown whether Runx2-overexpressing ADSCs (Runx2-ADSCs) could promote anterior cruciate ligament (ACL) reconstruction. We evaluated the effect of Runx2-ADSCs on ACL reconstruction in vitro and in vivo. mRNA expressions of osteocalcin (OCN), bone sialoprotein (BSP) and collagen I (COLI) increased over time in Runx2-ADSCs. Runx2 overexpression inhibited LPL and PPARγ mRNA expressions. Runx2 induced alkaline phosphatase activity markedly. In nude mice injected with Runx2-ADSCs, promoted bone formation was detected by X-rays 8 weeks after injection. The healing of tendon-to-bone in a rabbit model of ACL reconstruction treated with Runx2-ADSCs, fibrin glue only and an RNAi targeting Runx2, was evaluated with CT 3D reconstruction, histological analysis and biomechanical methods. CT showed a greater degree of new bone formation around the bone tunnel in the group treated with Runx2-ADSCs compared with the fibrin glue group and RNAi Runx2 group. Histology showed that treatment with Runx2-ADSCs led to a rapid and significant increase at the tendon-to-bone compared with the control groups. Biomechanical tests demonstrated higher tendon pullout strength in the Runx2-ADSCs group at early time points. The healing of the attachment in ACL reconstruction was enhanced by Runx2-ADSCs.

摘要

Runx2是一种强大的骨诱导因子，而脂肪来源干细胞（ADSCs）具有多能性。然而，过表达Runx2的ADSCs（Runx2-ADSCs）是否能促进前交叉韧带（ACL）重建尚不清楚。我们在体外和体内评估了Runx2-ADSCs对ACL重建的影响。Runx2-ADSCs中骨钙素（OCN）、骨涎蛋白（BSP）和I型胶原蛋白（COLI）的mRNA表达随时间增加。Runx2过表达抑制脂蛋白脂肪酶（LPL）和过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA表达。Runx2显著诱导碱性磷酸酶活性。在注射Runx2-ADSCs的裸鼠中，注射8周后通过X射线检测到骨形成得到促进。采用CT三维重建、组织学分析和生物力学方法，对仅用纤维蛋白胶和靶向Runx2的RNAi处理的Runx2-ADSCs治疗的ACL重建兔模型中腱骨愈合情况进行评估。CT显示，与纤维蛋白胶组和RNAi Runx2组相比，Runx2-ADSCs治疗组骨隧道周围新骨形成程度更高。组织学显示，与对照组相比，Runx2-ADSCs治疗导致腱骨处快速且显著增加。生物力学测试表明，Runx2-ADSCs组在早期时间点的腱拔出强度更高。Runx2-ADSCs增强了ACL重建中附着部位的愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/ae9e07fc292d/srep19073-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/a3d7b597e238/srep19073-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/64f097578be1/srep19073-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/4155c658c0df/srep19073-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/80827dd82411/srep19073-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/538197433d75/srep19073-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/0f8431ca6719/srep19073-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/c868bc4bac95/srep19073-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/ae9e07fc292d/srep19073-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/a3d7b597e238/srep19073-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/64f097578be1/srep19073-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/4155c658c0df/srep19073-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/80827dd82411/srep19073-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/538197433d75/srep19073-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/0f8431ca6719/srep19073-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/c868bc4bac95/srep19073-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2039/4705474/ae9e07fc292d/srep19073-f8.jpg

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