2. Academic Validation
  3. KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement

KAT6A/YAP/TEAD4 pathway modulates osteoclastogenesis by regulating the RANKL/OPG ratio on the compression side during orthodontic tooth movement

  • Prog Orthod. 2024 Aug 12;25(1):29. doi: 10.1186/s40510-024-00530-6.
Kuang Tan 1 2,  Jiayi Wang 1 2,  Xinyu Su 1 2,  Yunfei Zheng 3 4,  Weiran Li 5 6
Affiliations

Affiliations

  • 1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
  • 2 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China.
  • 3 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China. yunfei_zheng@bjmu.edu.cn.
  • 4 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. yunfei_zheng@bjmu.edu.cn.
  • 5 Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China. weiranli@bjmu.edu.cn.
  • 6 National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China. weiranli@bjmu.edu.cn.
PMID: 39129034 DOI: 10.1186/s40510-024-00530-6
Abstract

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.

Keywords

Acetylated YAP; KAT6A; Orthodontic tooth movement; Osteoclastogenesis; The RANKL/OPG ratio.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z