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人成骨样细胞增殖和分化过程中Wnt/β-连环蛋白信号相关细胞外拮抗剂的表达谱

Expression profiles of the Wnt/β-catenin signaling-related extracellular antagonists during proliferation and differentiation in human osteoblast-like cells.

作者信息

Parra-Torres Alma Y, Enríquez Juana, Jiménez-Ortega Rogelio F, Patiño Nelly, Castillejos-López Manuel De Jesús, Torres-Espíndola Luz M, Ramírez-Salazar Eric G, Velázquez-Cruz Rafael

机构信息

Genomics of Bone Metabolism Laboratory, National Institute of Genomic Medicine (INMEGEN), Mexico City 14610, Mexico.

Department of Reproduction Biology Carlos Gual Castro, National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), Mexico City 14080, Mexico.

出版信息

Exp Ther Med. 2020 Dec;20(6):254. doi: 10.3892/etm.2020.9384. Epub 2020 Oct 23.

Abstract

Bone formation is a dynamic process directed by osteoblast activity. The transition from the proliferation to differentiation stage during osteoblast maturation involves the downregulation of the Wnt/β-catenin signaling pathway, and extracellular antagonists are important for the regulation of Wnt signaling. However, the expression levels of Wnt antagonists in these stages of human osteoblast maturation have not been fully elucidated. Therefore, the aim of the present study was to investigate the expression levels of extracellular Wnt antagonists during proliferation and differentiation in osteoblast-like cell lines. The results demonstrated an overlap between the differential expression of secreted Frizzled-related protein ()2, , and Dickkopf ) 2 genes during the differentiation stage in the MG-63 and Saos-2 cells. Furthermore, high expression levels of in MG-63 cells, Wnt inhibitory factor 1 () in Saos-2 cells and in hFOB 1.19 cells during the same stage (differentiation), were observed. The upregulated expression levels of Wnt antagonists were also correlated with the high expression of during the differentiation stage. These findings suggested that Wnt-related antagonists could modulate the Wnt/β-catenin signaling pathway. By contrast, was the only gene that was found to be upregulated during the proliferation stage in hFOB 1.19 and Saos-2 cells. To the best of our knowledge, the present study provides, for the first time, the expression profile of Wnt antagonists during the proliferation stage and the initial phases of differentiation in osteoblast-like cell lines. The current results offer a basis to investigate potential targets for bone-related Wnt-signaling modulation in bone metabolism research.

摘要

骨形成是一个由成骨细胞活性主导的动态过程。成骨细胞成熟过程中从增殖阶段向分化阶段的转变涉及Wnt/β-连环蛋白信号通路的下调,细胞外拮抗剂对Wnt信号的调节很重要。然而,人成骨细胞成熟这些阶段中Wnt拮抗剂的表达水平尚未完全阐明。因此,本研究的目的是调查成骨样细胞系增殖和分化过程中细胞外Wnt拮抗剂的表达水平。结果表明,在MG-63和Saos-2细胞分化阶段,分泌型卷曲相关蛋白()2、、和Dickkopf)2基因的差异表达存在重叠。此外,在同一阶段(分化)观察到MG-63细胞中高表达,Saos-2细胞中Wnt抑制因子1()高表达,hFOB 1.19细胞中高表达。Wnt拮抗剂表达水平上调也与分化阶段的高表达相关。这些发现表明,Wnt相关拮抗剂可调节Wnt/β-连环蛋白信号通路。相比之下,是hFOB 1.19和Saos-2细胞增殖阶段唯一上调的基因。据我们所知,本研究首次提供了成骨样细胞系增殖阶段和分化初始阶段Wnt拮抗剂的表达谱。目前的结果为骨代谢研究中与骨相关的Wnt信号调节潜在靶点的研究提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a59a/7654218/17014c9ff2ef/etm-20-06-09384-g00.jpg

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