KAT6A/YAP/TEAD4 通路通过调节正畸牙齿移动过程中压迫侧的 RANKL/OPG 比率来调节破骨细胞生成。

IF 4.8 2区 医学 Q1 Dentistry
Kuang Tan, Jiayi Wang, Xinyu Su, Yunfei Zheng, Weiran Li
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引用次数: 0

摘要

背景:正畸牙齿移动(OTM)是一种动态平衡的骨重塑过程,涉及新骨的成骨和旧骨的破骨细胞生成,而这一过程是由机械力介导的。牙周韧带(PDL)间隙中的牙周韧带干细胞(PDLCS)可以在OTM过程中传递机械信号并调节破骨细胞的生成。KAT6A 是一种组蛋白乙酰转移酶,在干细胞的分化过程中发挥着作用。然而,KAT6A是否参与调控PDLSCs的破骨细胞生成仍不清楚:本研究利用力诱导OTM模型观察到,在OTM过程中PDL受压侧的KAT6A增加,体外受压的PDLSCs中KAT6A也增加。用 KAT6A 抑制剂 WM1119 抑制 KAT6A 能显著减少 OTM 的距离。敲除 PDLSCs 中的 KAT6A 可降低 RANKL/OPG 比率和 THP-1 的破骨细胞生成。从机制上讲,KAT6A通过结合和乙酰化YAP,同时调节YAP/TEAD轴和增加PDLSCs中的RANKL/OPG比率来促进破骨细胞生成。YAP-TEAD4相互作用抑制剂TED-347部分缓解了机械力诱导的RANKL/OPG比值升高:我们的研究表明,在机械力作用下,PDLSCs通过KAT6A/YAP/TEAD4途径调节破骨细胞生成并提高RANKL/OPG比率。KAT6A可能是加速OTM的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement.

Background: Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear.

Results: In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force.

Conclusion: Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM.

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来源期刊
Progress in Orthodontics
Progress in Orthodontics Dentistry-Orthodontics
CiteScore
7.30
自引率
4.20%
发文量
45
审稿时长
13 weeks
期刊介绍: Progress in Orthodontics is a fully open access, international journal owned by the Italian Society of Orthodontics and published under the brand SpringerOpen. The Society is currently covering all publication costs so there are no article processing charges for authors. It is a premier journal of international scope that fosters orthodontic research, including both basic research and development of innovative clinical techniques, with an emphasis on the following areas: • Mechanisms to improve orthodontics • Clinical studies and control animal studies • Orthodontics and genetics, genomics • Temporomandibular joint (TMJ) control clinical trials • Efficacy of orthodontic appliances and animal models • Systematic reviews and meta analyses • Mechanisms to speed orthodontic treatment Progress in Orthodontics will consider for publication only meritorious and original contributions. These may be: • Original articles reporting the findings of clinical trials, clinically relevant basic scientific investigations, or novel therapeutic or diagnostic systems • Review articles on current topics • Articles on novel techniques and clinical tools • Articles of contemporary interest
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