Regulatory T cell-exosomal miR-142-3p promotes angiogenesis and osteogenesis via TGFBR1/SMAD2 inhibition to accelerate fracture repair
Lang Chen, Yuan Xiong, Yiqiang Hu, Chenyan Yu, Adriana C. Panayi, Wu Zhou, Faqi Cao, Yun Sun, Mengfei Liu, Guodong Liu, Guodong Liu, Hang Xue, Liangcong Hu, Bobin Mi, Guohui Liu, Guohui Liu
Abstract
Although the immune system is well recognized as a key player in fracture repair, the exact mechanisms, particularly the role of regulatory T-cells (Tregs), have not yet been established. Our increased understanding of the Tregs and exosomes involved in organ repair creates opportunity of application of Tregs derived Exosomes (TregD-Exos) in the modulation of fracture repair. In the present study, we report that TregD-Exos containing miR-142-3p can be shuttled into bone mesenchymal stem cells (BMSCs) and Human umbilical vein endothelial cells (HUVECs) promoting osteogenesis and angiogenesis. Overexpression of miR-142-3p remarkedly promoted BMSC osteoblastic differentiation, and enhanced HUVEC function, including proliferation, migration and angiogenesis. Furthermore, TGFBR1/SMAD2 was shown to be involved in the TregD-Exos’ promotive effect on bone healing. Moreover, both TregD-Exos and miR-142-3p administration restored bone repair in vivo. Taken together, our results indicate that TregD-Exos containing miR-142-3p can be transferred to BMSCs and HUVECs with robust effects on osteogenesis and angiogenesis. These findings shed a new light for the use of Tregs in facilitating bone repair, suggesting that both TregD-Exos and miR-142-3p are promising effective therapeutic agents for bone remodeling.