微骨折技术联合间充质干细胞诱导剂抑制miR-708-5p靶向特殊的富含序列结合蛋白2,驱动兔膝骨关节炎软骨修复和再生。

IF 1.8 4区 生物学 Q4 CELL BIOLOGY
YongChao Wang, Qin Su, HaiRong Tang, Qiang Tian, Xin Lin, MeiChun Fu, RenMing Zhang, ZhangFeng Luo, KeYun Zhang
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引用次数: 0

摘要

膝关节骨性关节炎(KOA)是一种导致膝关节疼痛和功能限制的退行性关节疾病。在这项研究中,我们将微骨折手术与促进间充质干细胞(MSCs)分化的小生物活性分子kartogenin (KGN)结合起来,探索其对软骨修复的影响及其可能的潜在作用机制。本研究为KOA的临床治疗提供了一个全新的思路。采用微骨折技术联合KNG治疗家兔KOA模型。在关节内注射miR-708-5p和Special AT-rich sequence binding protein 2 (SATB2)慢病毒后,评估动物行为。随后检测肿瘤坏死因子α (TNF-α)、白细胞介素-1 (IL-1)的表达、滑膜组织和软骨组织的病理变化以及软骨II型胶原、MMP-1、MMP-3、TIMP-1的阳性表达。最后,通过荧光素酶实验验证miR-708-5p与SATB2的相互作用。我们的结果显示,miR-708-5p在兔KOA模型中升高;而SATB2的表达降低。同时,微骨折技术联合MSCs诱导剂KGN通过抑制miR-708-5p的表达来促进兔KOA软骨的修复和再生。我们还发现miR-708-5p直接靶向SATB2 mRNA调控其表达。此外,我们的数据表明,升高miR-708-5p或抑制SATB2可能逆转微骨折技术联合MSCs诱导剂对兔KOA的治疗效果。微骨折技术联合MSCs诱导剂抑制miR-708-5p靶向SATB2,驱动兔KOA软骨修复和再生。这表明微骨折技术联合MSCs诱导剂有望成为治疗骨关节炎的有效潜在方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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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来源期刊
Growth factors
Growth factors 生物-内分泌学与代谢
CiteScore
2.60
自引率
0.00%
发文量
20
审稿时长
>12 weeks
期刊介绍: Growth Factors is an international and interdisciplinary vehicle publishing new knowledge and findings on the regulators of cell proliferation, differentiation and survival. The Journal will publish research papers, short communications and reviews on current developments in cell biology, biochemistry, physiology or pharmacology of growth factors, cytokines or hormones which improve our understanding of biology or medicine. Among the various fields of study topics of particular interest include: •Stem cell biology •Growth factor physiology •Structure-activity relationships •Drug development studies •Clinical applications
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