The Role of Immune Cells in Orthodontic Tooth Movement

Method: Ni-Ti closed-coil-springs were set between upper-left-first-molar (M1) and upper-incisors of C57BL/6-mice in wild-type (WT) control-group and 8 experimental-groups (n=10/group) for 12 days:  NKs-depleted (NKs.dep), Ncr1-knockout (the Ncr1-gene was replaced by GFP [Ncr1^gfp/gfp]), Ncr1-heterozygote (Ncr1^+/gfp), NKG2D-blocked in WT-mice (WT/NKG2D.bl), NKG2D-blocked in Ncr1^gfp/gfp-mice (Ncr1^gfp/gfp/NKG2D.bl), CD4⁺-Ts–depleted (CD4⁺-Ts.dep), TNFα-knockout (TNFα^-/-) and IFNγ-knockout (IFNγ^-/-). A split-mouth-technique was used, in which M1-M2 distance was measured using μCT-scanner. Mice's maxillae were prepared for histology. The in-vivo accumulation of NKs in the periodontal-ligament (PDL) could be evaluated with the GFP presence in Ncr1^gfp/gfp and Ncr1^+/gfpmice. NKs' and Osteoclasts' number and location were evaluated using immunofluorescence and TRAP-stainings.  

Result: OTM was significantly reduced in NKs.dep, Ncr1^gfp/gfp, Ncr1^gfp/gfp/NKG2D.bl, CD4⁺-Ts.dep, TNFα^-/- and IFNγ^-/- groups (x1.49;x1.22;x4.31;x1.18;x3.30;x2.25 fold change, respectively, p<0.05), compared to WT, but was not changed in Ncr1^+/gfp or WT/NKG2D.bl. The number of GFP-labeled-NKs significantly increased in PDL of treated-teeth in comparison to contralateral side (x3.44, p<0.05). Osteoclasts number correlated with the M1-M2 distance in all groups (p<0.05).

Conclusion: OTM process in mice is mediated through Ncr1 and NKG2D receptors in NKs. Absence of NKs, Ncr1 and NKG2D-receptors, CD4⁺-Ts, TNFα and IFNγ significantly reduced the OTM-rate. NKs are accumulating in the PDL in response to orthodontic-force. Understanding the immune mechanisms involved in OTM will contribute to find novel therapeutic means to clinically control it.