Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway

Zou, Jian; Zhang, Wei; Li, Xin

doi:10.1007/s00223-016-0231-6

Cited by 18 publications

(17 citation statements)

References 29 publications

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“…Sclerostin overexpression significantly increased the expression levels of p16, p53 and p21, whereas, sclerostin knockdown decreased the expression levels of p16, p53 and p21. Although there had previously been no reports about the effect of sclerostin on the expression of p16, p53 and p21, it was believed that senescence acted as a tumor suppressor and sclerostin silence significantly increased the proliferation of osteosarcoma cells by promoting the progress of cell cycle in G1/S phase ( Zou, Zhang & Li, 2017 ). Thus, one can conclude that sclerostin may modulate the progression of HDPC senescence via both the p16 and p53 pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The deletion or down-regulation of sclerostin causes high bone mass diseases such as sclerosteosis ( Van Lierop et al, 2011 ) and Van Buchem disease ( Loots et al, 2005 ). As a well-known negative regulator of bone formation ( Zhang et al, 2016 ), sclerostin inhibits the proliferation and differentiation of cementoblasts ( Bao et al, 2013 ) and osteoprogenitor cells including osteosarcoma cells ( Zou, Zhang & Li, 2017 ) and human mesenchymal stem cells ( Sutherland et al, 2004 ). Recently, significantly elevated serum sclerostin was shown in the elderly ( Modder et al, 2011 ; Roforth et al, 2014 ), suggesting a possible role of sclerostin in aging-related bone loss as a result of decreased regenerative potential caused by the accumulation of senescent cells ( Farr et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Sclerostin promotes human dental pulp cells senescence

Ou¹,

Zhou²,

Liang³

2018

PeerJ

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BackgroundSenescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation.MethodsImmunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential.ResultsBy immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway.DiscussionThe increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sclerostin promotes human dental pulp cells senescence

Ou¹,

Zhou²,

Liang³

2018

PeerJ

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“…Since MG-63 cells exhibit certain characteristics of osteoblasts and U2OS cells are more malignant and stable than MG-63 cells, U2-OS cells were selected for western blot analysis ( 14 ). A total Protein Extraction kit (Beyotime Institute of Biotechnology, Haimen, China) was used to extract the total protein from U2OS cells, according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

Combined application of Embelin and tumor necrosis factor-related apoptosis-inducing ligand inhibits proliferation and invasion in osteosarcoma cells via caspase-induced apoptosis

et al. 2018

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Embelin, as an inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), may induce apoptosis in various types of cancer cells. The present study aimed to determine the effect of Embelin on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of osteosarcoma cells. Embelin and TRAIL were applied to U2OS and MG63 cells, respectively or in combination. MTT was initially used to detect the difference in survival rates between the group receiving combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin and the individual application groups. Light microscopic quantification was used to detect the morphology of the osteosarcoma cells in each group. Determination of cell apoptosis was subsequently performed using flow cytometry. The invasive ability of the cells was detected by a Transwell assay, prior to relative protein expression being determined by western blot analysis. Based on all the test data, it was revealed that the survival rates and the invasive ability were significantly lower following the combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin than following the individual application of either (P<0.01). Additionally, upregulating expression of caspases, as well as death receptor 5, and downregulating expression of XIAP and matrix metalloproteinase 9 (MMP-9), had more significant effects in the combined group compared with the individual group and the control group. All these results suggested that Embelin may enhance TRAIL-induced apoptosis and inhibit the invasion of human osteosarcoma cells.

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“…Studies have revealed that MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and MMP-13 are significantly related to osteosarcoma metastasis and poor prognosis [ 19 , 33 – 38 ]. To identify the mediator of MCP-1-promoted osteosarcoma migration, we further examined the expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and MMP-13 mRNA under MCP-1 stimulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

Liu

Chen

Chang³

et al. 2020

J Exp Clin Cancer Res

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Background Osteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed. Methods The osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro. Results The present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens. Conclusions Our results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.

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Effects of SOST Gene Silencing on Proliferation, Apoptosis, Invasion, and Migration of Human Osteosarcoma Cells Through the Wnt/β-Catenin Signaling Pathway

Cited by 18 publications

References 29 publications

Sclerostin promotes human dental pulp cells senescence

Sclerostin promotes human dental pulp cells senescence

Combined application of Embelin and tumor necrosis factor-related apoptosis-inducing ligand inhibits proliferation and invasion in osteosarcoma cells via caspase-induced apoptosis

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

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