Kong Ruina, Gao Jie, Zhang Ju, Ji Lianmei, Yu Yiyi, Zhang Lanling, Zhao Dongbao
Department of Rheumatology & Immunology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Future Med Chem. 2022 Jan;14(2):81-96. doi: 10.4155/fmc-2021-0177. Epub 2021 Dec 20.
Synovial mesenchymal stem cell (SMSC)-derived exosomes show treatment potential in osteoarthritis, although their functional mechanism is still unclear. Osteoarthritis chondrocytes and normal SMSC were cultured. Subsequently, chondrocytes were co-cultured with SMSC or -overexpressing SMSC-derived exosomes, or directly transfected with mimic. Furthermore, compensate experiments were conducted. SMSC promoted chondrocyte proliferation, migration, COL2A1 and ACAN expressions while suppressing apoptosis by transmitting exosomes. Furthermore, -overexpressing SMSC-derived exosomes and direct overexpression in chondrocytes presented more significant effect on enhancing chondrogenesis. In addition, directly targeted ADAM19, and ADAM19 overexpression compensated the regulation of on chondrogenesis. SMSC-derived exosomal enhances chondrogenesis through targeting ADAM19, highlighting a potentially novel mechanism of SMSC in treating osteoarthritis.
滑膜间充质干细胞(SMSC)衍生的外泌体在骨关节炎中显示出治疗潜力,尽管其功能机制仍不清楚。培养骨关节炎软骨细胞和正常SMSC。随后,将软骨细胞与SMSC或过表达SMSC衍生的外泌体共培养,或直接用模拟物转染。此外,进行了补偿实验。SMSC通过传递外泌体促进软骨细胞增殖、迁移、COL2A1和ACAN表达,同时抑制细胞凋亡。此外,过表达SMSC衍生的外泌体和在软骨细胞中直接过表达对增强软骨形成有更显著的作用。此外,直接靶向ADAM19,ADAM19过表达补偿了对软骨形成的调节。SMSC衍生的外泌体通过靶向ADAM19增强软骨形成,突出了SMSC治疗骨关节炎的潜在新机制。