Zhou Xinghua, Liang Hansi, Hu Xiaohan, An JinNan, Ding Sisi, Yu Shuichang, Liu Cuiping, Li Fang, Xu Yunyun
Institute of Pediatrics, Children's Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, China.
Cell Death Discov. 2020 Dec 10;6(1):142. doi: 10.1038/s41420-020-00374-z.
In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and exosomes may play a major role. Here, we acquired a special kind of MSCs from the bone marrow of surgically resected tissue from the hand of a patient with polydactyly. Experiments were focused on the role of polydactyly bone marrow-derived MSCs (pBMSCs) in osteoarthritis. The results showed that the pBMSCs had a greater ability than the BMSCs to differentiate into chondrocytes. Mechanistically, the expression of BMP4 was significantly higher in the pBMSCs than it was in the BMSCs. Furthermore, we showed that the migration and proliferation of chondrocytes were stimulated by exosomes secreted by pBMSC (pBMSC-EXOs). Notably, the downregulation of BMP4 in pBMSCs by siRNA inhibited both the chondrogenic differentiation potential of the MSCs and the function of the chondrocytes. In addition, the injection of pBMSC-EXOs and BMSC-EXOs attenuated OA in an OA mouse model, but the pBMSC-EXOs had a superior therapeutic effect compared with that of the BMSC-EXOs. Taken together, the data indicate that pBMSCs have greater ability to differentiate into chondrocytes and regulate chondrocyte formation through BMP4 signaling. Therefore, pBMSC-EXOs may represent a novel treatment for OA.
在过去十年中,间充质干细胞(MSCs)已被广泛用于治疗骨关节炎(OA),外泌体可能发挥主要作用。在此,我们从一名多指患者手部手术切除组织的骨髓中获取了一种特殊的MSCs。实验聚焦于多指骨髓来源的间充质干细胞(pBMSCs)在骨关节炎中的作用。结果表明,pBMSCs比骨髓间充质干细胞(BMSCs)具有更强的向软骨细胞分化的能力。机制上,pBMSCs中骨形态发生蛋白4(BMP4)的表达明显高于BMSCs。此外,我们发现pBMSC分泌的外泌体(pBMSC-EXOs)可刺激软骨细胞的迁移和增殖。值得注意的是,通过小干扰RNA(siRNA)下调pBMSCs中BMP4的表达,可抑制间充质干细胞的软骨形成分化潜能以及软骨细胞的功能。此外,在骨关节炎小鼠模型中,注射pBMSC-EXOs和BMSC-EXOs均可减轻骨关节炎,但与BMSC-EXOs相比,pBMSC-EXOs具有更好的治疗效果。综上所述,数据表明pBMSCs具有更强的向软骨细胞分化的能力,并通过BMP4信号通路调节软骨细胞的形成。因此,pBMSC-EXOs可能代表一种治疗骨关节炎的新方法。