title: Using a novel microRNA delivery system to inhibit osteoclastogenesis.
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.
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. yaoylan@126.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. yaoylan@126.com.
authors: Yanlan
authors: Y
authors: Yao
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. jtt216@126.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. jtt216@126.com.
authors: Tingting
authors: T
authors: Jia
authors: Institute for Infectious Disease and Endemic Disease Control, Beijing Center for Disease Prevention and Control (CDC), Beijing 100013, China. panyang10@gmail.com.
authors: Yang
authors: Y
authors: Pan
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. gogo2026@126.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. gogo2026@126.com.
authors: Hongna
authors: H
authors: Gou
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. 13552566721@139.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. 13552566721@139.com.
authors: Yulong
authors: Y
authors: Li
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. ysunchina@163.com.
authors: Yu
authors: Y
authors: Sun
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. zrzxd@sina.com.
authors: Rui
authors: R
authors: Zhang
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. sarahkuo@163.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. sarahkuo@163.com.
authors: Kuo
authors: K
authors: Zhang
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. linguigao1982@163.com.
authors: Guigao
authors: G
authors: Lin
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. jhxie@nccl.org.cn.
authors: Jiehong
authors: J
authors: Xie
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. jmli63hn@gmail.com.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. jmli63hn@gmail.com.
authors: Jinming
authors: J
authors: Li
authors: National Center for Clinical Laboratories, Beijing Hospital, No. 1 Dahua Road, Dongdan, Beijing 100730, China. lnwang@nccl.org.cn.|Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 9 Santiao, Dongdan, Beijing 100730, China. lnwang@nccl.org.cn.
authors: Lunan
authors: L
authors: Wang
mesh_terms: D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D035683:MicroRNAs / Q000235:genetics*; D010010:Osteoclasts / Q000502:physiology*; D048029:TNF Receptor-Associated Factor 6 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D035683:MicroRNAs; D048029:TNF Receptor-Associated Factor 6; C512478:EGFR protein, human; D066246:ErbB Receptors