Effect of a DPP‐4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption

Abstract

Objectives. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used as a treatment for type 2 diabetes mellitus and have also recently been applied to enhance bone quality and density, and increase the expression of bone markers. This study aimed to investigate the effect of a DPP-4 inhibitor on orthodontic tooth movement (OTM) and related root resorption in a mouse model. Materials and Methods. Mice were randomly divided into three groups: those undergoing OTM with the addition of a DPP-4 inhibitor (30 μg), those undergoing OTM and receiving phosphate-buffered saline (PBS), and those without force loading (control group). OTM was achieved by means of a nickel–titanium closed coil spring that moved the first molar in a mesial direction for 12 days. The distance of OTM was measured using silicone impression. Maxillae were removed for histological analysis or real-time PCR analysis. Results. The distance of OTM and the number of osteoclasts were significantly decreased after administration of the DPP-4 inhibitor, which also significantly suppressed the number of odontoclasts and root resorption after OTM. Furthermore, the mRNA expression of tumour necrosis factor-α (TNF-α) and the receptor activator of nuclear factor kappa-B ligand (RANKL) were decreased in DPP-4 inhibitor-treated mice compared with those receiving PBS and control animals. Conclusion. The DPP-4 inhibitor inhibited tooth movement and associated root resorption by blocking the formation of osteoclasts and odontoclasts, respectively. It also appeared to inhibit osteoclastogenesis and odontoclastogenesis by suppressing the expression of TNF-α and/or RANKL.

Tumor necrosis factor-α enhances the expression of vascular endothelial growth factor in a mouse orthodontic tooth movement model

“…1 ). 26 , 27 , 28 , 29 , 30 According to manufacturer's instructions, the Ni–Ti closed coil spring has a 10 g force. OTM was carried out for 12 days.…”

“…At this point decrease the cutting thickness to 4 μm and proceed sectioning all the way to the apex of the root. 27 , 29 The sections were deparaffinized and hydrated through xylenes and decreasing concentrations of graded ethanol series. For VEGF staining, the sections were immersed in 0.3% H 2 O 2 in PBS for 15 min and were blocked with blocking solution (5% skim milk, 0.05% Triton X-100, 3% bovine serum albumin in PBS) for 30 min at 37 °C.…”

“…Total RNA was isolated and purified from samples using RNeasy Mini Kit (Qiagen, Valencia, CA, USA) as described previously. 29 cDNA synthesized from 2 μg of total RNA was used for cDNA synthesizing by SuperScript IV Reverse Transcriptase (Invitrogen). TB Green Premix Ex Taq II (Takara, Shiga, Japan) with the Thermal Cycler Dice Real Time System (Takara) were used for real-time PCR.…”

Effects of Incretin-Related Diabetes Drugs on Bone Formation and Bone Resorption

“…Using a mouse model of OTM involving the application of a nickel–titanium closed coil spring to move the first molar in the mesial direction for 12 days, we showed that local administration of linagliptin significantly reduced the amount of OTM, the numbers of osteoclasts and odontoclasts, and the extent of root resorption [ 66 ]. In addition, the levels of TNF-α and RANKL mRNA expression were also reduced in the linagliptin-treated mice in our study, consistent with the anti-inflammatory effects of DPP-4 inhibitors reported previously in a number of different types of vascular cells and immune cells [ 162 , 163 ].…”

“…A position statement published more than a decade ago by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) approved the use of DPP-4 inhibitors and GLP-1R agonists in treatment of type 2 diabetes and as second-line agents for treatment of poor glycemic control [ 63 ]. We showed previously that the DPP-4 inhibitor, linagliptin, and the GLP-1R agonist, exendin-4, attenuated osteoclast formation and bone resorption in vivo in a mouse model of lipopolysaccharide (LPS)-induced inflammation [ 64 , 65 ], and both of these agents were shown to inhibit mechanical stress-induced osteoclast formation and bone resorption in a mouse model of orthodontic tooth movement [ 66 , 67 ].…”