title: Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway.
abstract: Our study explored the effects of SOST gene silencing on the proliferation, apoptosis, invasion, and migration of human osteosarcoma cells through Wnt/β-catenin signaling pathway. Fresh tissues were obtained from 108 patients with osteosarcoma and 46 patients with osteochondroma. Human osteosarcoma cells (MG-63, U2-OS, HOS, and Saos-2) and normal osteoblast (hFoB1.19) were selected and cultured. Osteosarcoma cells were grouped randomly into the blank group, the scrambled control group, and the SOST-siRNA group. Cell proliferation was determined by MTT assay. Cell cycle and apoptosis were tested by flow cytometry. Transwell and scratch test were performed to determine cell invasion and migration. The qRT-PCR and Western blotting were used to detect mRNA and protein expression level of sclerostin, Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7. The activity of caspase-3 was assessed by immunocytochemistry. Alkaline phosphatase (ALP) activity was measured using P-nitrophenylphosphate as a substrate. Low SOST mRNA and sclerostin protein expression levels were observed in osteosarcoma tissues and cells. Compared with the blank and scrambled control groups, sclerostin expression, apoptotic cells, ALP activity, and caspase-3 activity were down-regulated, while the proliferation, invasion, and migration abilities of osteosarcoma cells were evidently enhanced in the SOST-siRNA group. After SOST gene silencing, the mRNA and protein expression levels of Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7 in osteosarcoma cells and β-catenin protein expression levels in the nucleus and cytoplasm were significantly elevated. SOST gene silencing promotes the proliferation, invasion, and migration, and inhibits apoptosis of osteosarcoma cells by activating Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, 200233, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, 200233, People's Republic of China. wei_zhang_wz@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai, 200233, People's Republic of China. xiaolin_Lii@163.com.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics*; D002648:Child; D005260:Female; D020868:Gene Silencing; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C495270:CTNNB1 protein, human; D005819:Genetic Markers; C422903:SOST protein, human; D051176:beta Catenin
keywords: Osteosarcoma cells; SOST gene silencing; Wnt/β-catenin signaling pathway