Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH),Molecular Biology Reports

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Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH)
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2023-04-07 , DOI: 10.1007/s11033-023-08411-7
Hai-Jia Xu ₁ , Xiang-Zhong Liu ₁ , Lu Yang ₂ , Yu Ning ₃ , Liang-Liang Xu ₄ , Da-Ming Sun ₄ , Wen Liao ₁ , Yi Yang ₄ , Zhang-Hua Li ₁

Affiliation

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.

中文翻译：

Runx2过表达促进股骨头坏死（ONFH）的骨修复

背景

Runt 相关转录因子 2 (Runx2) 被认为是提高间充质干细胞 (MSC) 骨修复能力的诱导剂。

方法和结果

24只家兔用于建立股骨头坏死（ONFH），随机分为四组：腺病毒Runx2（Ad-Runx2）组、Runx2-siRNA组、MSCs组和模型组。造模1周后，Ad-Runx2组注射5×107个Ad-Runx2转染MSCs，Runx2-siRNA组注射5×107个Runx2-siRNA转染MSCs，MSCs组注射5 × 107 未处理的 MSCs，模型组用生理盐水处理。在模型建立后1周和3周进行注射。注射MSCs后3周和6周检测股骨头骨形态发生蛋白2（BMP-2）、Runx2和Osterix的表达，马松三色染色、大体形态学、X线及CT影像观察评价ONFH的修复效果。数据显示，Runx2-siRNA组BMP-2、Runx2、Osterix的表达在3周时较MSCs组有所降低，6周时进一步降低，但仍高于Model组，此外奥斯特里克斯；Ad-Runx2组这三个基因的表达量高于MSCs组。Masson三色染色、大体形态学及X-ray和CT图像观察显示，MSCs组坏死股骨头较Runx2-siRNA组股骨头塌陷不规则更规则、光滑。Ad-Runx2组坏死的股骨头基本得到完全修复，并被丰富的软骨和骨组织覆盖。Runx2-siRNA组中Runx2和Osterix在3周时较MSCs组有所降低，6周后表达进一步降低，但除Osterix外仍高于Model组；Ad-Runx2组这三个基因的表达量高于MSCs组。Masson三色染色、大体形态学及X-ray和CT图像观察显示，MSCs组坏死股骨头较Runx2-siRNA组股骨头塌陷不规则更规则、光滑。Ad-Runx2组坏死的股骨头基本得到完全修复，并被丰富的软骨和骨组织覆盖。Runx2-siRNA组中Runx2和Osterix在3周时较MSCs组有所降低，6周后表达进一步降低，但除Osterix外仍高于Model组；Ad-Runx2组这三个基因的表达量高于MSCs组。Masson三色染色、大体形态学及X-ray和CT图像观察显示，MSCs组坏死股骨头较Runx2-siRNA组股骨头塌陷不规则更规则、光滑。Ad-Runx2组坏死的股骨头基本得到完全修复，并被丰富的软骨和骨组织覆盖。但除Osterix外仍高于Model组；Ad-Runx2组这三个基因的表达量高于MSCs组。Masson三色染色、大体形态学及X-ray和CT图像观察显示，MSCs组坏死股骨头较Runx2-siRNA组股骨头塌陷不规则更规则、光滑。Ad-Runx2组坏死的股骨头基本得到完全修复，并被丰富的软骨和骨组织覆盖。但除Osterix外仍高于Model组；Ad-Runx2组这三个基因的表达量高于MSCs组。Masson三色染色、大体形态学及X-ray和CT图像观察显示，MSCs组坏死股骨头较Runx2-siRNA组股骨头塌陷不规则更规则、光滑。Ad-Runx2组坏死的股骨头基本得到完全修复，并被丰富的软骨和骨组织覆盖。