PDGF-AA promotes cell-to-cell communication in osteocytes through PI3K/Akt signaling pathway

PDGF-AA promotes cell-to-cell communication in osteocytes through PI3K/Akt signaling pathway
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PDGF-AA通过PI3K/Akt信号通路促进骨细胞细胞间通讯

DOI:
10.1093/abbs/gmab136
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发表时间:
2021-12-01
影响因子:
3.7
通讯作者:
Xie,Jing
Xie,Jing
中科院分区:
生物学3区
文献类型:
--
作者:
Liu,Yang;Duan,Mengmeng;Xie,Jing

文献摘要

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骨细胞是骨重塑中的主要敏感细胞,因为它们具有从矿化骨基质到骨表面和骨髓的有效功能细胞过程。邻近的骨细胞通过这些细胞过程相互通讯,通过间隙连接通道实现分子交换。据报道,血小板源性生长因子-AA (PDGF-AA) 可通过促进类骨细胞谱系中的细胞增殖、迁移和自分泌分泌来增强骨组织重塑。然而,PDGF-AA对骨细胞间通讯的影响仍不清楚。在本研究中,我们阐明PDGF-AA可以通过促进连接蛋白43(Cx43)的表达来增强骨细胞树突状突起的形成和间隙连接细胞间通讯。该调节过程主要依赖于磷脂酰肌醇 3 激酶 (PI3K)/Akt(也称为蛋白激酶 B,PKB)信号传导对 Akt 蛋白磷酸化的激活。抑制 PI3K/Akt 信号传导可降低 PDGF-AA 诱导的 Cx43 表达。这些结果在PDGF-AA和骨细胞中的细胞间通讯之间建立了一座桥梁,这可以帮助我们了解骨细胞之间的分子交换和骨折愈合。
Osteocytes are the main sensitive cells in bone remodeling due to their potent functional cell processes from the mineralized bone matrix to the bone surface and the bone marrow. Neighboring osteocytes communicate with each other by these cell processes to achieve molecular exchange through gap junction channels. Platelet-derived growth factor-AA (PDGF-AA) has been reported to enhance bone tissue remodeling by promoting cell proliferation, migration, and autocrine secretion in osteoid cell linage. However, the effect of PDGF-AA on intercellular communication between osteocytes is still unclear. In the present study, we elucidated that PDGF-AA could enhance the formation of dendritic processes of osteocytes and the gap junctional intercellular communication by promoting the expression of connexin43 (Cx43). This modulation process was mainly dependent on the activation of phosphorylation of Akt protein by phosphatidylinositol 3-kinase (PI3K)/Akt (also known as protein kinase B, PKB) signaling. Inhibition of PI3K/Akt signaling decreased the Cx43 expression induced by PDGF-AA. These results establish a bridge between PDGF-AA and cell–cell communication in osteocytes, which could help us understand the molecular exchange between bone cells and fracture healing.