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.