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 os...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 micro RNA transcriptome after compression stress and focused on micro RNA146 a-5 p(mi R-146 a),which was significantly decreased by compression.Transfection of an inhibitor of mi R-146 a stimulated angiogenesis of HUVECs while mi R-146 a mimics repressed angiogenesis.Adiponectin(ADP)was confirmed to be a target of mi R-146 a 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 mi R-146 a observed in osteoclasts after compression promotes angiogenesis by targeting ADP,suggesting a novel method to interfere with bone remodeling induced by compression stress.展开更多
基金financially supported by grants from the National Natural Science Foundation of China(81700938,81670957)。
文摘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 micro RNA transcriptome after compression stress and focused on micro RNA146 a-5 p(mi R-146 a),which was significantly decreased by compression.Transfection of an inhibitor of mi R-146 a stimulated angiogenesis of HUVECs while mi R-146 a mimics repressed angiogenesis.Adiponectin(ADP)was confirmed to be a target of mi R-146 a 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 mi R-146 a observed in osteoclasts after compression promotes angiogenesis by targeting ADP,suggesting a novel method to interfere with bone remodeling induced by compression stress.
