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Compression loading of osteoclasts attenuated microRNA-146a-5p expression, which promotes angiogenesis by targeting adiponectin

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Abstract

Osteoclastogenesis in alveolar bone induced by compression stress triggers orthodontic tooth movement. Compression stress also stimulates angiogenesis, which is essential for osteoclastogenesis. However, the effects of osteoclastogenesis induced by compression on angiogenesis are poorly understood. In vivo, we found the markers of angiogenesis increased during orthodontic bone remodeling. In vitro, osteoclast-derived exosomes increased proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as expression of vascular endothelial growth factor and CD31. The promotive effects of exosomes derived from compressed osteoclasts were greater than those derived from osteoclasts without compression. Next, we analyzed changes in the microRNA transcriptome after compression stress and focused on microRNA146a-5p (miR-146a), which was significantly decreased by compression. Transfection of an inhibitor of miR-146a stimulated angiogenesis of HUVECs while miR-146a mimics repressed angiogenesis. Adiponectin (ADP) was confirmed to be a target of miR-146a by dual luciferase reporter assay. In HUVECs treated with exosomes, we detected increased ADP which promoted angiogenesis. Knockdown of ADP in HUVECs reduced the promotive effects of exosomes. Our results demonstrate that the decreased miR-146a observed in osteoclasts after compression promotes angiogenesis by targeting ADP, suggesting a novel method to interfere with bone remodeling induced by compression stress.

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Acknowledgements

This work was financially supported by grants from the National Natural Science Foundation of China (81700938, 81670957). The funders had no role in study design, data collection and analysis, decision to publish, or the preparation of the article.

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  1. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China

    Yue Wang, Yunfei Zheng & Weiran Li

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  1. Yue Wang
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  2. Yunfei Zheng
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Correspondence to Yunfei Zheng or Weiran Li.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The results of microRNA sequencing are available on www.ncbi.nlm.nih.gov/Traces/study/?acc=PRJNA629042&o=acc_s%3Aa.

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The author(s) declare that they have no conflict of interest. Animal experimental protocols were approved by the Animal Use and Care Committee of Peking University (LA2020033).

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Wang, Y., Zheng, Y. & Li, W. Compression loading of osteoclasts attenuated microRNA-146a-5p expression, which promotes angiogenesis by targeting adiponectin. Sci. China Life Sci. 65, 151–166 (2022). https://doi.org/10.1007/s11427-020-1869-7

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