microRNA-21 Contributes to Orthodontic Tooth Movement

• Published in: Journal of dental research 2016-11, Vol.95 (12), p.1425-1433
• Main Authors: Chen, N., Sui, B.D., Hu, C.H., Cao, J., Zheng, C.X., Hou, R., Yang, Z.K., Zhao, P., Chen, Q., Yang, Q.J., Jin, Y., Jin, F.
• Format: Article
• Language: English
• Subjects: Alveolar bone; Alveolar Bone Loss - physiopathology; Alveolar Process - physiology; Animals; Apoptosis; Bone growth; Bone loss; Bone marrow; Bone remodeling; Bone Remodeling - physiology; Bone resorption; c-Fos protein; Cell death; Cell differentiation; Dentistry; Humans; Immune system; Immunohistochemistry; Inflammation; Ligaments; Lipopolysaccharides; Maxilla; Mesenchymal stem cells; Mice; Mice, Inbred C57BL; Microenvironments; MicroRNAs; MicroRNAs - metabolism; miRNA; mRNA; Orthodontics; Osteoblastogenesis; Osteoblasts - physiology; Osteoclastogenesis; Osteogenesis; Osteogenesis - physiology; Periodontal ligament; Periodontal Ligament - cytology; Periodontium; Phenotypes; Post-transcription; Real-Time Polymerase Chain Reaction; Stem cell transplantation; Stem cells; Stress, Mechanical; Studies; Teeth; Tooth Movement Techniques
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034516657043

microRNAs could be mechanosensitive and emerge as critical posttranscriptional regulators in the bone-remodeling process. During orthodontic tooth movement (OTM), the application of mechanical force induces alveolar bone remodeling, but whether microRNAs respond to orthodontic force and contribute to OTM is unknown. microRNA-21 (miR-21) has been previously reported in vitro to mediate stretch-induced osteogenic differentiation of periodontal ligament stem cells and support osteoclast differentiation. In this study, the authors show that miR-21 responded to orthodontic force in periodontal tissue in a dose- and time-dependent manner and regulated the osteogenesis of human periodontal ligament stem cells following OTM. Using mmu-miR-21-deficient (miR-21-/-) mice, the authors discovered that mmu-miR-21 deficiency inhibited OTM and prevented force-induced maxillary bone loss. The authors found that miR-21-/- mice showed a normal skeletal phenotype in development and a similar alveolar bone formation rate to wild-type mice postnatally. During OTM, mmu-miR-21 regulated force-induced alveolar osteoblastogenesis in the tensile side, while no effects were detected in the compressive side. However, miR-21-/- mice showed inhibited alveolar osteoclastogenesis when compared with wild-type mice. During OTM, mmu-miR-21 deficiency blocked alveolar bone resorption in both the compressive and tensile sides. To dissect the mechanism by which miR-21 regulates alveolar bone remodeling, the authors screened the reported functional targets of miR-21 and found that periodontal expression of programmed cell death 4 (Pdcd4) was inhibited following OTM. Furthermore, mmu-miR-21 deficiency removed the suppression of Pdcd4 at both the mRNA and protein levels in the periodontium, resulting in upregulation of the downstream effector C-fos. Further analysis of OTM under lipopolysaccharide-induced periodontal inflammation showed that mmu-miR-21 mediated lipopolysaccharide (LPS)-accelerated OTM and that mmu-miR-21 deficiency blocked lipopolysaccharide-induced maxillary bone loss. In summary, these findings reveal a previously unrecognized mechanism that a microRNA can modulate OTM and alveolar bone remodeling under both normal and inflammatory microenvironments in vivo.