title: M1-like Macrophage Polarization Promotes Orthodontic Tooth Movement.
abstract: Macrophages play a crucial role in inflammatory-mediated bone loss. Orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. However, whether and how macrophages contribute to mechanical force-induced OTM remains unknown. In this study, we hypothesized that polarization of M1-like macrophages may contribute to the OTM. Orthodontic nickel-titanium springs were applied to the upper first molars of rats or mice to induce OTM. The distance of OTM gradually increased after mechanical force was applied to the rats for 5 and 10 d. M1-like macrophage polarization and expression of M1 cytokine tumor necrosis factor (TNF)-α also increased after force application. More importantly, monocyte/macrophage depletion in mice by injection of clodronate liposomes decreased the distance of OTM and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68(+) macrophages, accompanied by reduced expressions of M1 markers TNF-α and inducible nitric oxide synthase (iNOS), whereas systemic transfusion of M1 macrophages in mice increased them. Further experiments showed that injection of recombinant TNF-α increased the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as upregulated the expression of TNF-α and iNOS. Blockage of TNF-α by etanercept injection reduced the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as decreased the levels of TNF-α and iNOS. These data suggest that M1-like macrophage polarization promotes alveolar bone resorption and consequent OTM after mechanical force application.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: D
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Kou
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Q
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, P.R. China yanhengzhou@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009970:Orthodontics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014087:Tooth Movement Techniques; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D055114:X-Ray Microtomography
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: biomechanical phenomena; bone resorption; inflammation; macrophage activation; orthodontics; osteoclasts