PDGF-AA promotes gap junction intercellular communication in chondrocytes via the PI3K/Akt pathway.

IF 2.8 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2022-09-01 Epub Date: 2022-02-12 DOI:10.1080/03008207.2022.2036733

Siqun Xu, Yang Liu, Demao Zhang, Hongcan Huang, Jiachi Li, Jieya Wei, Yueyi Yang, Yujia Cui, Jing Xie, Xuedong Zhou

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引用次数: 3

Abstract

Background: Gap junction intercellular communication (GJIC) plays an important role in cell growth, development and homeostasis. Connexin 43 (Cx43) is an important half-channel protein responsible for gap junction formation. Platelet-derived growth factor AA (PDGF-AA) regulates the proliferation, migration, metabolism, apoptosis and cell cycle of chondrocytes. However, the role of PDGF-AA in gap junction intercellular communication in chondrocytes is not fully understood. In the current study, we performed experiments to explore the effect of PDGF-AA on GJIC and its underlying biomechanical mechanism.

Methods: qPCR was performed to determine the expression of PDGF, PDGFR and connexin family genes in chondrocytes and/or cartilage. A scrape loading/dye transfer assay was used to determine GJIC. Western blot analysis was applied to detect the expression of Cx43 and PI3K/Akt signaling pathway proteins. Immunofluorescence staining was utilized to examine protein distribution. Scanning electron microscopy was used to delineate the morphology of chondrocytes.

Results: Expression of PDGF-A mRNA was highest among the PDGF family in chondrocytes and cartilage tissues. PDGF-AA promoted functional GJIC formation in chondrocytes by upregulating the expression of Cx43. Enhanced functional GJIC formation in chondrocytes induced by PDGF-AA occurred through the activation of PI3K/Akt signaling and its nuclear accumulation.

Conclusion: For the first time, this study provides evidence demonstrating the role of PDGF-AA in cell-to-cell communication in chondrocytes through mediating Cx43 expression.

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PDGF-AA通过PI3K/Akt通路促进软骨细胞间隙连接的细胞间通讯。

背景:间隙连接细胞间通讯(GJIC)在细胞生长、发育和体内平衡中起着重要作用。Connexin 43 (Cx43)是一种重要的半通道蛋白，负责缝隙连接的形成。血小板衍生生长因子AA (platelet derived growth factor AA, PDGF-AA)调节软骨细胞的增殖、迁移、代谢、凋亡和细胞周期。然而，PDGF-AA在软骨细胞间隙连接细胞间通讯中的作用尚不完全清楚。在本研究中，我们通过实验探讨PDGF-AA对GJIC的影响及其潜在的生物力学机制。方法:采用qPCR方法检测PDGF、PDGFR和连接蛋白家族基因在软骨细胞和/或软骨中的表达。采用刮载/染料转移法测定GJIC。Western blot检测Cx43和PI3K/Akt信号通路蛋白的表达。免疫荧光染色检测蛋白分布。用扫描电镜观察软骨细胞的形态。结果:PDGF家族中PDGF- a mRNA在软骨细胞和软骨组织中表达最高。PDGF-AA通过上调Cx43的表达促进软骨细胞功能性GJIC的形成。PDGF-AA通过激活PI3K/Akt信号及其核积累，诱导软骨细胞功能性GJIC形成增强。结论:本研究首次提供了PDGF-AA通过介导Cx43表达参与软骨细胞间通讯的证据。

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

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.