LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-catenin.
LATS1/YAP1 Axis Controls Bone Regeneration on Distraction Osteogenesis by Activating Wnt/β-catenin.
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DOI：
10.1089/ten.tea.2023.0091
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发表时间：
2023-11
影响因子：
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通讯作者：
Kehan Li;Linan Liu;Hanghang Liu;Jiawei Xing;Pei Hu;Jian Song
中科院分区：
文献类型：
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作者：
Kehan Li;Linan Liu;Hanghang Liu;Jiawei Xing;Pei Hu;Jian Song
河马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是河马信号通路的核心组成部分，与淋巴管侵袭、星形胶质细胞增生症、细胞凋亡和自噬有关。然而，HIPPO/LATS1在成骨过程中的作用仍不清楚。在这里，我们使用核糖核酸(RNA)慢病毒来抑制Lats1在大鼠骨髓来源干细胞(BMSCs)和牵张成骨区域的表达。在Lats1抑制的BMSCs中，观察到BMSCs的成骨、增殖和迁移能力增强，而YAP1抑制可以部分逆转这些表型。在体内，我们发现LATS1/YAP1轴在牵张成骨(DO)过程中促进成骨。β-连环蛋白与其在体内和体外的表达呈正相关。当yap1在胞核呈强阳性时，β-catenin表达上调，当yap1表达被维替普芬抑制时，β-catenin在胞核不表达。这些发现表明，LATS1/YAP1信号轴通过激活Wnt/β-Catenin信号通路促进DO的发生。本研究通过LATS1/YAP1-β-Catenin的联合作用，为DO成骨的分子机制和潜在的骨再生治疗策略提供了新的思路。
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. Here, 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 osteogenesis's molecular mechanism and a potential therapeutic strategy for bone regeneration in DO by associating with LATS1/YAP1-β-catenin.