title: microRNA-21 Contributes to Orthodontic Tooth Movement.
abstract: 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.
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|2 Department of Orthodontics, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: N
authors.initials: N
authors.lastname: Chen
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: B D
authors.initials: BD
authors.lastname: Sui
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Hu
authors.affiliation: 2 Department of Orthodontics, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: C X
authors.initials: CX
authors.lastname: Zheng
authors.affiliation: 4 Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: R
authors.initials: R
authors.lastname: Hou
authors.affiliation: 2 Department of Orthodontics, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Z K
authors.initials: ZK
authors.lastname: Yang
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 2 Department of Orthodontics, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 5 Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Q J
authors.initials: QJ
authors.lastname: Yang
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|3 Xi'an Institute of Tissue Engineering and Regenerative Medicine, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.affiliation: 1 Center for Tissue Engineering, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.|2 Department of Orthodontics, State Key Laboratory of Military Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: F
authors.initials: F
authors.lastname: Jin
mesh_terms: D016301:Alveolar Bone Loss / Q000503:physiopathology; D000539:Alveolar Process / Q000502:physiology*; D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D013314:Stress, Mechanical; D014087:Tooth Movement Techniques
chemical_list: D008070:Lipopolysaccharides; D035683:MicroRNAs
keywords: bone remodeling; epigenetic repression; inflammation; mesenchymal stromal cells; osteoclasts; osteogenesis