LATS1/YAP1轴通过激活Wnt/β-catenin控制牵张成骨过程中的骨再生。

IF 3.5 3区 医学 Q3 CELL & TISSUE ENGINEERING
Tissue Engineering Part A Pub Date : 2024-02-01 Epub Date: 2023-12-14 DOI:10.1089/ten.TEA.2023.0091
Kehan Li, Linan Liu, Hanghang Liu, Jiawei Xing, Pei Hu, Jian Song
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引用次数: 0

摘要

Hippo信号通路抑制细胞生长,其成分和功能在哺乳动物中高度保守。LATS1是Hippo信号通路的核心成分,与淋巴侵袭、星形胶质细胞增生、细胞凋亡和自噬有关。然而,Hippo/LATS1在成骨中的作用尚不清楚。在这里,我们使用核糖核酸(RNA)慢病毒来抑制大鼠骨髓源性干细胞(BMSCs)和牵张成骨区域中Lats1的表达。在Lats1抑制的BMSCs中观察到BMSCs的成骨、增殖和迁移能力增加,而YAP1抑制部分逆转了这些表型。在体内,我们发现LATS1/YAP1轴在牵张成骨(DO)过程中促进了成骨。β-catenin与YAP1的体内外表达呈正相关。当YAP1在细胞核中强阳性时,β-catenin的表达上调;当维替泊芬抑制YAP1的表达时,β-catenin在细胞核中不表达。这些发现表明,LATS1/YAP1信号轴通过激活Wnt/β-catenin信号通路来促进DO。本研究通过与LATS1/YAP1-β-连环蛋白的结合,深入了解了DO成骨的分子机制和骨再生的潜在治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-Catenin.

The Hippo signaling pathway inhibits cell growth, and its components and functions are highly conserved in mammals. LATS1 is a core component of the Hippo signaling pathway associated with lymphatic invasion, astrogliosis, apoptosis, and autophagy. Nevertheless, the role of Hippo/LATS1 in osteogenesis remains unclear. In this study, we used ribonucleic acid (RNA) lentiviruses to inhibit the expression of Lats1 in bone marrow-derived stem cells (BMSCs) and distraction osteogenic regions in rats. Increased osteogenic, proliferative, and migratory abilities of BMSCs were observed in Lats1-inhibited BMSCs, while these phenotypes were partially reversed by YAP1 inhibition. In vivo, we found that the LATS1/YAP1 axis promoted osteogenesis during distraction osteogenesis (DO). β-catenin was positively correlated with YAP1 expression in vivo and in vitro. When YAP1 was strongly positive in the nucleus, β-catenin expression was upregulated; when YAP1 expression was inhibited by verteporfin, β-catenin was not expressed in the nucleus. These findings suggest that the LATS1/YAP1 signaling axis promotes DO by activating the Wnt/β-catenin signaling pathway. This study provides insights into the molecular mechanism of osteogenesis and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-β-catenin.

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来源期刊
Tissue Engineering Part A
Tissue Engineering Part A Chemical Engineering-Bioengineering
CiteScore
9.20
自引率
2.40%
发文量
163
审稿时长
3 months
期刊介绍: Tissue Engineering is the preeminent, biomedical journal advancing the field with cutting-edge research and applications that repair or regenerate portions or whole tissues. This multidisciplinary journal brings together the principles of engineering and life sciences in the creation of artificial tissues and regenerative medicine. Tissue Engineering is divided into three parts, providing a central forum for groundbreaking scientific research and developments of clinical applications from leading experts in the field that will enable the functional replacement of tissues.
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