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Runx2 过表达促进股骨头坏死(ONFH)的骨修复。

Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH).

机构信息

Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, 430060, China.

Department of Anesthesiology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, 430060, China.

出版信息

Mol Biol Rep. 2023 Jun;50(6):4769-4779. doi: 10.1007/s11033-023-08411-7. Epub 2023 Apr 7.

DOI:10.1007/s11033-023-08411-7
PMID:37029290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10209270/
Abstract

BACKGROUND

Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs).

METHODS AND RESULTS

Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue.

CONCLUSIONS

Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.

摘要

背景

runt 相关转录因子-2(Runx2)被认为是一种诱导物,可提高间充质干细胞(MSCs)的骨修复能力。

方法和结果

24 只兔子用于建立股骨头坏死(ONFH),并随机分为四组:腺病毒 Runx2(Ad-Runx2)组、Runx2-siRNA 组、MSCs 组和模型组。在模型建立后 1 周,Ad-Runx2 组用转染 Ad-Runx2 的 5×107 MSCs 治疗,Runx2-siRNA 组用转染 Runx2-siRNA 的 5×107 MSCs 治疗,MSCs 组注射 5×107 未经处理的 MSCs,模型组用生理盐水治疗。注射分别在模型建立后 1 周和 3 周进行。在 MSCs 注射后 3 周和 6 周检测股骨头的骨形态发生蛋白 2(BMP-2)、Runx2 和 Osterix 的表达,并通过 Masson 三色染色、大体形态、X 线和 CT 图像观察评估 ONFH 的修复效果。数据显示,Runx2-siRNA 组在 3 周时的 BMP-2、Runx2 和 Osterix 表达低于 MSCs 组,6 周时进一步降低,但仍高于模型组除 Osterix 外;Ad-Runx2 组中这三个基因的表达均高于 MSCs 组。Masson 三色染色、大体形态和 X 线及 CT 图像观察显示,MSCs 组坏死的股骨头比 Runx2-siRNA 组更规则、更光滑,其股骨头塌陷且不规则。在 Ad-Runx2 组中,坏死的股骨头基本完全修复,被丰富的软骨和骨组织覆盖。

结论

Runx2 的过表达可以改善 MSCs 的成骨表型维持,并促进 ONFH 的坏死骨修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/00c0acd4a01e/11033_2023_8411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/79601693eb80/11033_2023_8411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/dab2518d158b/11033_2023_8411_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/00c0acd4a01e/11033_2023_8411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/79601693eb80/11033_2023_8411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/dab2518d158b/11033_2023_8411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/6c5713d9e341/11033_2023_8411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/97429387ca9a/11033_2023_8411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/393d/10209270/00c0acd4a01e/11033_2023_8411_Fig5_HTML.jpg

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