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异体脂肪间充质干细胞促进兔软骨细胞再分化标志物的表达并延缓膝骨关节炎的进展。

Allogeneic adipose-derived mesenchymal stem cells promote the expression of chondrocyte redifferentiation markers and retard the progression of knee osteoarthritis in rabbits.

作者信息

Zhang Rui, Meng Fanbo, Zhang Qiaoxia, Zou Zhiyu, Xiao Kunlin, Zhu Tian, Li Hui, Zhang Weijie, Ma Jie, Ma Jianbing

机构信息

Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University Xi'an, Shaanxi, China.

Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University Xi'an, Shaanxi, China.

出版信息

Am J Transl Res. 2021 Feb 15;13(2):632-645. eCollection 2021.

Abstract

Osteoarthritis (OA) is a progressively degenerative disease of joints. culture of chondrocytes results in dedifferentiation, which is characterized by the development of fibroblast phenotypes, reduced ability to produce cartilage extracellular matrix (ECM) and increase the expression of molecular markers Col1a1, Col10a1 and Runx2. Redifferentiation of chondrocytes is indicated by increased expression of the molecular markers Col2a1, Aggrecan and Sox9. In the current study, we investigated the effects of allogeneic rabbit adipose-derived mesenchymal stem cells (ADSCs) on articular chondrocytes, and explored the therapeutic effect of ADSCs on damaged articular cartilage at different stages in a rabbit OA model. , the proliferation and migration of primary articular chondrocytes were enhanced by cocultured rabbit ADSCs, and the expression of redifferentiation markers in chondrocytes cocultured with ADSCs was increased at both the mRNA and protein levels, while the expression of dedifferentiation markers was decreased. , the rabbit model of OA was established by anterior cruciate ligament transection (ACLT) with complete medial meniscectomy (MMx). Two weeks after surgery, ADSCs were used for OA rabbit treatment. Intra-articular injection of ADSCs gradually alleviated articular cartilage destruction, decreased Osteoarthritis Research Society International (OARSI) and Mankin scores, and reduced MMP13 expression at different stages in the rabbit model of OA. During the experiment, allogeneic ADSCs did not cause any adverse events. The current study demonstrates the effects and molecular mechanisms of ADSCs on articular chondrocytes and provides a favorable reference for clinical OA treatment with mesenchymal stem cells (MSCs) derived from adipose tissue.

摘要

骨关节炎(OA)是一种进行性关节退行性疾病。软骨细胞培养会导致去分化,其特征是成纤维细胞表型的发展、产生软骨细胞外基质(ECM)的能力降低以及分子标志物Col1a1、Col10a1和Runx2的表达增加。软骨细胞的再分化表现为分子标志物Col2a1、聚集蛋白聚糖和Sox9的表达增加。在本研究中,我们研究了同种异体兔脂肪间充质干细胞(ADSCs)对关节软骨细胞的影响,并探讨了ADSCs对兔OA模型不同阶段受损关节软骨的治疗作用。共培养兔ADSCs可增强原代关节软骨细胞的增殖和迁移,与ADSCs共培养的软骨细胞中再分化标志物在mRNA和蛋白质水平上的表达均增加,而去分化标志物的表达则降低。通过切断前交叉韧带(ACLT)并完全切除内侧半月板(MMx)建立兔OA模型。术后两周,使用ADSCs对OA兔进行治疗。关节内注射ADSCs可逐渐减轻关节软骨破坏,降低国际骨关节炎研究学会(OARSI)和曼金评分,并降低兔OA模型不同阶段的MMP13表达。在实验过程中,同种异体ADSCs未引起任何不良事件。本研究证明了ADSCs对关节软骨细胞的作用及其分子机制,为临床应用脂肪组织来源的间充质干细胞(MSCs)治疗OA提供了有利参考。

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