Transforming Growth Factor-β Signaling Inhibits the Osteogenic Differentiation of Mesenchymal Stem Cells via Activation of Wnt/β-Catenin Pathway.

Q2 Medicine
Journal of Bone Metabolism Pub Date : 2025-02-01 Epub Date: 2025-02-28 DOI:10.11005/jbm.24.761
Mahsa Tahoori, Azita Parvaneh Tafreshi, Fatemeh Naghshnejad, Bahman Zeynali
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引用次数: 0

Abstract

Background: Due to the contradictory and temporally variable effects of transforming growth factor-β (TGF-β) and the Wnt/β-catenin pathways on osteogenic differentiation in different stem cell types, we sought to examine the activity of these pathways as well as their interaction during the osteogenic differentiation of the osteo-induced adiposederived mesenchymal stem cells (AD-MSCs).

Methods: The osteo-induced AD-MSCs were treated with TGF-β1 (1 ng/mL) either alone or together with its antagonist SB- 431542 (10 μM) or that of the Wnt antagonist, inhibitor of Wnt production 2 (IWP2) (3 μM), every 3 days for 21 days. Cells were then analyzed for calcium deposit, bone matrix production, and the osteogenic markers gene expression.

Results: Our results showed firstly that, either of the pathways is active since the mRNA expressions of their respective target genes, PAI-1 and Cyclin D1 were detectable although the latter was at a very low level. Secondly that, treatment with TGF-β1 decreased levels of calcium deposit, bone matrix production and the osteogenic markers gene expression. Accordingly, osteogenesis was induced in those treated with SB either alone or together with the TGF-β1, pointing to inhibitory effect of TGF-β pathway on osteogenic differentiation. Thirdly that following treatment with IWP2 and TGF-β1, the inhibitory effect of TGF-β1 on bone matrix production was reversed. Fourthly, there was constantly low expression of Wnt3amRNA but progressively increasing that of its endogenous antagonist Dkk-1mRNA throughout.

Conclusions: Together these results suggest that TGF-β1 requires the active Wnt/β-catenin signaling pathway to exert its inhibitory effects on osteogenic differentiation of AD-MSCs.

转化生长因子-β 信号通过激活 Wnt/β-Catenin 通路抑制间充质干细胞的成骨分化
背景:由于转化生长因子-β (TGF-β)和Wnt/β-catenin通路对不同类型干细胞成骨分化的影响相互矛盾且具有时间性,我们试图研究这些通路的活性及其在骨诱导脂肪源性间充质干细胞(AD-MSCs)成骨分化过程中的相互作用。方法:用TGF-β1 (1 ng/mL)单独或联合其拮抗剂SB- 431542 (10 μM)或Wnt拮抗剂、Wnt生成抑制剂2 (IWP2) (3 μM)处理成骨诱导的AD-MSCs,每3 d处理一次,共21 d。然后分析细胞钙沉积、骨基质生成和成骨标志物基因表达。结果:我们的研究结果首先表明,这两条通路都是有活性的,因为它们各自的靶基因PAI-1和Cyclin D1的mRNA表达都可以检测到,尽管后者的表达水平很低。其次,TGF-β1治疗可降低钙沉积水平、骨基质生成及成骨标志物基因表达。由此可见,SB单独或联合TGF-β1均能诱导成骨,提示TGF-β通路对成骨分化有抑制作用。第三,用IWP2和TGF-β1治疗后,TGF-β1对骨基质生成的抑制作用被逆转。第四,Wnt3amRNA在整个过程中持续低表达,而其内源性拮抗剂Dkk-1mRNA的表达逐渐增加。结论:综上所述,TGF-β1需要激活Wnt/β-catenin信号通路才能发挥其抑制AD-MSCs成骨分化的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Bone Metabolism
Journal of Bone Metabolism Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
3.70
自引率
0.00%
发文量
23
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