title: MicroRNA-106b inhibits osteoclastogenesis and osteolysis by targeting RANKL in giant cell tumor of bone.
abstract: Giant cell tumor (GCT) of bone consists of three major cell types: giant cells, monocytic cells, and stromal cells. From microarray analysis, we found that miR-106b was down-regulated in GCT clinical samples and further determined by fluorescence in situ hybridization. In addition, the expression of novel potential target of miR-106b, RANKL, was elevated in GCT along with previously determined targets in other tumors such as IL-8, MMP2 and TWIST. In a RANKL 3'UTR luciferase reporter assays, agomiR-106b repressed the luciferase activity and the effect was eliminated when the targeting site in the reporter was mutated, suggesting a direct regulation of miR-106b on RANKL mRNA. Moreover, overexpression of miR-106b in GCTSCs through TALEN-mediated site-specific knockin clearly inhibited osteoclastogenesis and osteolysis. By grafting the GCT onto the chick CAM, we confirmed the inhibitory effect of miR-106b on RANKL expression and giant cell formation. Furthermore, in an OVX mouse model, silencing of miR-106b increased RANKL protein expression and promoted bone resorption, while up-regulation of miR-106b inhibited bone resorption. These results suggest that miR-106b is a novel suppressor of osteolysis by targeting RANKL and some other cytokines, which indicates that miR-106b may be a potential therapeutic target for the treatment of GCT.
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Huabin
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Anatomy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhenxi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Anatomy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Zhi'an
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wangjun
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tielong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xinghai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D002648:Child; D005260:Female; D005818:Genetic Engineering; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010014:Osteolysis; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D053245:RANK Ligand
keywords: RANKL; giant cell tumor of bone; miR-106b; osteoclastogenesis; osteolysis