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Int. J. Mol. Sci. 2015, 16(4), 8337-8350; doi:10.3390/ijms16048337

Using a Novel MicroRNA Delivery System to Inhibit Osteoclastogenesis

1,2,†
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1
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1,2,* and 1,2,*
1
National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China
2
Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China
3
Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control (CDC), Beijing 100013, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Nicholas Delihas
Received: 1 March 2015 / Revised: 25 March 2015 / Accepted: 1 April 2015 / Published: 14 April 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3573 KB, uploaded 14 April 2015]   |  

Abstract

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. View Full-Text
Keywords: MS2 VLP; miR-146a; rheumatoid arthritis; osteoporosis; osteoclast MS2 VLP; miR-146a; rheumatoid arthritis; osteoporosis; osteoclast
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yao, Y.; Jia, T.; Pan, Y.; Gou, H.; Li, Y.; Sun, Y.; Zhang, R.; Zhang, K.; Lin, G.; Xie, J.; Li, J.; Wang, L. Using a Novel MicroRNA Delivery System to Inhibit Osteoclastogenesis. Int. J. Mol. Sci. 2015, 16, 8337-8350.

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