A new strategy for controlling tooth movement using the hematogenous stem cell supply system: toward the development of nucleic acid drugs

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ishida Yuji 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00516297)
• Co-Investigator(Kenkyū-buntansha): 細道 純 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00420258)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: SDF-1 / ケモカイン / 矯正的歯の移動 / 中和抗体 / 血行性細胞集積

Outline of Final Research Achievements

To elucidate the mechanism of hematogenous stem cell supply to periodontal ligament (PDL) during orthodontic tooth movement (OTM) and to explore pharmacological control of OTM through the regulation of this mechanism, this study used a fluorescently labeled bone marrow cell transplantation model to investigate how OTM and the cell supply mechanism are interrupted by SDF-1 neutralizing antibody. Results showed increased SDF-1 expression and osteoclast accumulation in the PDL on compression side, but the transplanted fluorescent-labeled hematogenous cells were not detected. On the other hand, local administration of SDF-1 neutralizing antibody had a short-lasting inhibitory effect on OTM and osteoclast accumulation in the PDL, but no change in SDF-1 levels in the peripheral blood. Additionally, it was also found that OTM was quickly restored after administration was interrupted. These results suggest that OTM can be controlled by using SDF-1 neutralizing antibodies.

Free Research Field

矯正歯科学

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、矯正的歯の移動において、歯根膜圧迫側におけるSDF-1発現が上昇すること、局所的な破骨細胞集積に局所のSDF-1が関与していること、抗SDF-1中和抗体の局所投与により歯の移動を抑制できること、中和抗体の効果が非常に短期であり投与中断により速やかに薬理効果が切れること、中和抗体の局所投与による全身性の影響が少ないことが明らかとなった。これらの知見は、SDF-1が将来的な歯の矯正的移動について薬理学的コントロールする治療法を開発する際のターゲット分子となる可能性が期待できる結果となり、将来の効率的で安定した矯正治療法の開発の一助になると思われる。