Sun Xiangyi, Long Ruchao, Chen Qiang, Feng Jian, Gao Yang, Zhu Guangqi, Yang Zhihua
Department of Orthopedics, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311200, China.
Cell Biochem Biophys. 2025 Mar;83(1):1277-1288. doi: 10.1007/s12013-024-01561-w. Epub 2024 Oct 7.
This study aims to elucidate the role of miR-378a-3p in facilitating the proliferation and differentiation of synovium-derived mesenchymal stem cells (SMSCs) into chondrocytes. The effects of overexpressing miR-378a-3p on SMSCs were investigated through histological analysis, quantitative PCR, and western blotting. Then we identified binding sites of miR-378a-3p with BMP2 through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and predictions from the RegRNA 2.0 database. Subsequently, BMP2 was confirmed as the target by which miR-378a-3p promotes the chondrogenic differentiation of SMSCs using a luciferase reporter gene assay and an miR-378a-3p RNA interference plasmid. Finally, by constructing a rat model with articular cartilage damage, we detected the reparative effects of miR-378a-3p overexpression on cartilage damage. Additionally, we verified the mechanism by which miR-378a-3p promotes chondrogenic differentiation in SMSCs. MiR-378a-3p enhances the proliferation and differentiation of SMSCs into chondrocytes by modulating the BMP2-Smad signaling pathway, thereby facilitating repair processes for articular cartilage injuries in rats. Notably, knockdown of BMP2 diminished the reparative efficacy of miR-378a-3p on articular cartilage damage. Upregulation of miR-378a-3p promotes chondrogenic differentiation in SMSCs through activation of the BMP2-Smad pathway, positioning it as a potential therapeutic target for osteoarthritis.
本研究旨在阐明miR-378a-3p在促进滑膜来源的间充质干细胞（SMSCs）增殖并分化为软骨细胞过程中的作用。通过组织学分析、定量PCR和蛋白质印迹法研究了过表达miR-378a-3p对SMSCs的影响。然后，我们通过基因本体论、京都基因与基因组百科全书分析以及RegRNA 2.0数据库的预测，确定了miR-378a-3p与骨形态发生蛋白2（BMP2）的结合位点。随后，使用荧光素酶报告基因检测法和miR-378a-3p RNA干扰质粒，证实BMP2是miR-378a-3p促进SMSCs软骨形成分化的靶点。最后，通过构建大鼠关节软骨损伤模型，我们检测了miR-378a-3p过表达对软骨损伤的修复作用。此外，我们还验证了miR-378a-3p促进SMSCs软骨形成分化的机制。miR-378a-3p通过调节BMP2-Smad信号通路增强SMSCs增殖并分化为软骨细胞，从而促进大鼠关节软骨损伤的修复过程。值得注意的是，敲低BMP2会降低miR-378a-3p对关节软骨损伤的修复效果。miR-378a-3p的上调通过激活BMP2-Smad通路促进SMSCs的软骨形成分化，使其成为骨关节炎的潜在治疗靶点。
