title: Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.
abstract: Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
authors.forename: M
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Haidian District, 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, Haidian District, Beijing, P.R. China Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000145:classification*; D008297:Male; D008963:Molar / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009969:Orthodontic Wires / Q000009:adverse effects; D010010:Osteoclasts / Q000473:pathology; D010513:Periodontal Ligament / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis; D051116:Receptors, Scavenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D012391:Root Resorption / Q000473:pathology*; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D014087:Tooth Movement Techniques / Q000009:adverse effects* / Q000295:instrumentation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D000135:Acid Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000068800:Etanercept; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007371:Interferon-gamma; D016753:Interleukin-10; D015847:Interleukin-4; D007527:Isoenzymes; D052247:Nitric Oxide Synthase Type II; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D018124:Receptors, Tumor Necrosis Factor; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C496318:Nos2 protein, rat
keywords: biomechanical phenomena; bone remodeling; inflammation; macrophage activation; orthodontics; phenotype