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Microfracture technique combined with mesenchymal stem cells inducer represses miR-708-5p to target special at-rich sequence-binding protein 2 to drive cartilage repair and regeneration in rabbit knee osteoarthritis

软骨 间充质干细胞 骨关节炎 诱导剂 再生(生物学) 肿瘤坏死因子α 信使核糖核酸 荧光素酶 癌症研究 医学 基质金属蛋白酶 细胞生物学 病理 免疫学 生物 转染 解剖 内科学 生物化学 基因 替代医学
作者
Yongchao Wang,Qin Su,Haiping Tang,Qiang Tian,Xiangmin Lin,Meichun Fu,RenMing Zhang,Zewei Luo,K W Zhang
出处
期刊:Growth Factors Journal [Informa]
卷期号:41 (3): 115-129
标识
DOI:10.1080/08977194.2023.2227269
摘要

Knee osteoarthritis (KOA) is a degenerative joint illness which leads to knee pain and functional limitation. In this study, we combined microfracture surgery with kartogenin (KGN), a small bioactive molecule used to promote the differentiation of mesenchymal stem cells (MSCs), and explored its impact on cartilage repair and possible latent mechanisms of action. The research offers a brand-new idea for the clinical cure of KOA. The microfracture technique in combination with KNG treatment was performed on a rabbit model of KOA. Animal behaviour was evaluated after the intra-articular injection of miR-708-5p and Special AT-rich sequence binding protein 2 (SATB2) lentiviruses. Later, the expression of the tumour necrosis factor α (TNF-α) and interleukin- 1 (IL-1), the pathology of synovial tissue and cartilage tissue, and the positive cartilage type II collagen, MMP-1, MMP-3 and TIMP-1 were detected. Finally, a luciferase assay was conducted to verify the interaction of miR-708-5p and SATB2. Our results showed that miR-708-5p was elevated in the rabbit KOA model; however, the expression of SATB2 was reduced. Meanwhile, the microfracture technology combined with MSCs inducer KGN drove cartilage repair and regeneration in rabbit KOA by repressing the miR-708-5p expression. We also found that miR-708-5p directly targeted the SATB2 mRNA to regulate its expression. Furthermore, our data urged that elevating miR-708-5p or restraining SATB2 may reverse the therapeutic effect of the microfracture technique combined with MSCs inducer on rabbit KOA. Microfracture technique combined with MSCs inducer represses miR-708-5p to target SATB2 to drive cartilage repair and regeneration in rabbit KOA. This indicates that the microfracture technique combined with MSCs inducers is supposed to be an effective latent method for osteoarthritis cure.

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