Exosomes from Microvascular Endothelial Cells under Mechanical Unloading Inhibit Osteogenic Differentiation via miR-92b-3p/ELK4 Axis.
Exosomes from Microvascular Endothelial Cells under Mechanical Unloading Inhibit Osteogenic Differentiation via miR-92b-3p/ELK4 Axis.
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DOI：
10.3390/jpm12122030
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发表时间：
2022-12-08
影响因子：
--
通讯作者：
Shi, Fei
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoyan;Zhang, Lijun;Xu, Liqun;Li, Gaozhi;Wang, Ke;Xue, Tong;Sun, Quan;Tang, Hao;Cao, Xinsheng;Hu, Zebing;Zhang, Shu;Shi, Fei
Mechanical unloading-related bone loss adversely harms astronauts’ health. Nevertheless, the specific molecular basis underlying the phenomenon has not been completely elucidated. Although the bone microvasculature contributes significantly to bone homeostasis, the pathophysiological role of microvascular endothelial cells (MVECs) in bone loss induced by mechanical unloading is not apparent. Here, we discovered that MC3T3-E1 cells could take up exosomes produced by MVECs under clinorotation-unloading conditions (Clino Exos), which then prevented MC3T3-E1 cells from differentiating into mature osteoblasts. Moreover, miR-92b-3p was found to be highly expressed in both unloaded MVECs and derived exosomes. Further experiments demonstrated that miR-92b-3p was transferred into MC3T3-E1 cells by exosomes, resulting in the suppression of osteogenic differentiation, and that encapsulating miR-92b-3p inhibitor into the Clino Exos blocked their inhibitory effects. Furthermore, miR-92b-3p targeted ELK4 and the expression of ELK4 was lessened when cocultured with Clino Exos. The inhibitor-92b-3p-promoted osteoblast differentiation was partially reduced by siRNA-ELK4. Exosomal miR-92b-3p secreted from MVECs under mechanical unloading has been shown for the first time to partially attenuate the function of osteoblasts through downregulation of ELK4, suggesting a potential strategy to protect against the mechanical unloading-induced bone loss and disuse osteoporosis.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
破骨细胞来源的外泌体 miR-214-3p 抑制成骨细胞骨形成
影响因子：
16.6
作者：
Li D;Liu J;Guo B;Liang C;Dang L;Lu C;He X;Cheung HY;Xu L;Lu C;He B;Liu B;Shaikh AB;Li F;Wang L;Yang Z;Au DW;Peng S;Zhang Z;Zhang BT;Pan X;Qian A;Shang P;Xiao L;Jiang B;Wong CK;Xu J;Bian Z;Liang Z;Guo DA;Zhu H;Tan W;Lu A;Zhang G
通讯作者：
Zhang G
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
3.7
作者：
Blaber EA;Dvorochkin N;Lee C;Alwood JS;Yousuf R;Pianetta P;Globus RK;Burns BP;Almeida EA
通讯作者：
Almeida EA
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G