Using a Novel MicroRNA Delivery System to Inhibit Osteoclastogenesis

International Journal of Molecular Sciences

Yanlan Yao²  Tingting Jia²  Yang Pan¹  Hongna Gou²  Yulong Li²  Yu Sun²  Rui Zhang²  Kuo Zhang²  Guigao Lin²  Jiehong Xie²  Jinming Li²  Lunan Wang² 

[1] Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control (CDC), Beijing 100013, China; E-Mail:;National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China; E-Mails:

关键词: MS2 VLP;    miR-146a;    rheumatoid arthritis;    osteoporosis;    osteoclast;   

DOI  :  10.3390/ijms16048337

来源: mdpi

【 摘 要 】

Previously, we developed a novel microRNA (miRNA) delivery system based on bacteriophage MS2 virus-like particles (MS2 VLPs). In this current study, we used this system to transport miR-146a into human peripheral blood mononuclear cells (PBMCs), and demonstrated the inhibition of osteoclastogenesis in precursors. Two cytokines, receptor activator of NF-κB ligand (RANKL), and macrophage-colony stimulating factor (M-CSF) were used to induce osteoclastogenesis. MS2 VLPs were transfected into PBMCs. qRT-PCR was applied to measure expression levels of miR-146a and osteoclast (OC)-specific genes. Western blot (WB) was conducted to evaluate miR-146a downstream target proteins: epidermal growth factor receptor (EGFR) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). The formation and activity of OCs were assessed by cytochemical staining and bone resorption assay, respectively. In PBMCs treated with MS2-miR146a VLPs, qRT-PCR assays showed increased expression of miR-146a (p < 0.01) and decreased expression of all four OC-specific genes (p < 0.05). WB results indicated decreased expression of EGFR (p < 0.01) and TRAF6 (p < 0.05). The number of OCs decreased markedly and bone resorption assay demonstrated inhibited activity. This miR-146a delivery system could be applied to induce overexpression of miR-146a and to inhibit the differentiation and function of OCs.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.