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源自过表达Runx2的骨髓间充质干细胞的外泌体增强软骨组织再生并预防兔模型中的膝关节骨关节炎。

Exosomes Derived from Runx2-Overexpressing BMSCs Enhance Cartilage Tissue Regeneration and Prevent Osteoarthritis of the Knee in a Rabbit Model.

作者信息

Hu Jing, Shi Zheng-Shuai, Liu Xiang-Zhong, Cai Han-Tao, Yang Ao-Fei, Sun Da-Ming, Xu Liang-Liang, Yang Yi, Li Zhang-Hua

机构信息

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430015, China.

Huanggang Hospital of TCM Affiliated to Hubei University of Chinese Medicine, Huanggang 438000, China.

出版信息

Stem Cells Int. 2022 Nov 28;2022:6865041. doi: 10.1155/2022/6865041. eCollection 2022.

Abstract

OBJECTIVES

Osteoarthritis is the leading disease of joints worldwide. Osteoarthritis may be treated by exosomes derived from Runx2-overexpressed bone marrow mesenchymal stem cells (R-BMSCs-Exos). R-BMSCs-Exos would promote the proliferation, migration, and phenotypic maintenance of articular chondrocytes.

METHODS

BMSCs were transfected with and without Runx2. Exosomes derived from BMSCs and R-BMSCs (BMSCs-Exos and R-BMSCs-Exos) were isolated and identified. Proliferation, migration, and phenotypic maintenance were determined and compared between groups. The mechanism for activation of Yes-associated protein (YAP) was investigated using small interfering RNA (siRNA). The exosomes' preventive role was determined using Masson trichrome and immunohistochemical staining.

RESULTS

R-BMSCs-Exos enhance the proliferation, migration, and phenotypic maintenance of articular chondrocytes based on the YAP being activated. R-BMSCs-Exos prevent knee osteoarthritis as studied through a rabbit model.

CONCLUSIONS

Findings emphasize the efficacy of R-BMSCs-Exos in preventing osteoarthritis. Potential source of exosomes is sorted out for the advantages and shortcomings. The exosomes are then modified based on the molecular mechanisms to address their limitations. Such exosomes derived from modified cells have the role in future therapeutics.

摘要

目的

骨关节炎是全球主要的关节疾病。骨关节炎可用源自过表达Runx2的骨髓间充质干细胞(R-BMSCs-Exos)的外泌体进行治疗。R-BMSCs-Exos可促进关节软骨细胞的增殖、迁移和表型维持。

方法

对骨髓间充质干细胞进行有无Runx2的转染。分离并鉴定源自骨髓间充质干细胞和R-BMSCs的外泌体(BMSCs-Exos和R-BMSCs-Exos)。测定并比较各组之间的增殖、迁移和表型维持情况。使用小干扰RNA(siRNA)研究Yes相关蛋白(YAP)的激活机制。通过Masson三色染色和免疫组织化学染色确定外泌体的预防作用。

结果

基于YAP被激活,R-BMSCs-Exos增强关节软骨细胞的增殖、迁移和表型维持。通过兔模型研究发现,R-BMSCs-Exos可预防膝骨关节炎。

结论

研究结果强调了R-BMSCs-Exos在预防骨关节炎方面的疗效。对外泌体的潜在来源进行了优缺点梳理。然后根据分子机制对其进行修饰以解决其局限性。这种源自修饰细胞的外泌体在未来治疗中具有作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecf5/11401735/3501443df1af/SCI2022-6865041.001.jpg

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