Susceptibility of different mouse strains to peri-implantitis

Abstract

Background and objective: Peri-implantitis (PI) is an inflammatory condition that affects the tissues surrounding dental implants. Although the pathogenesis of PI is not fully understood, evidence suggests that the etiology is multifactorial and may include a genetic component. The aim of this study was to investigate the role of genetics in the development of peri-implantitis.

Material and methods: Four-week-old C57BL/6J, C3H/HeJ and A/J male mice had their left maxillary molars extracted. Implants were placed in the healed extraction sockets. Upon osseointegration, ligatures were placed around the implant head for 1 or 4 weeks to induce PI. Micro-computed tomography scanning was used to measure volumetric bone loss. Histological analyses were also performed to evaluate collagen organization and the presence of neutrophils and osteoclasts.

Results: Radiographically, comparing the ligature-treated mice, C57BL/6J displayed the greatest amount of bone loss, followed by C3H/HeJ and A/J mice at 1 and 4 weeks. Histologically, at 1 week, C57BL/6J mice presented with the highest numbers of neutrophils and osteoclasts. At 4 weeks, C57BL/6J mice presented with the most active bone remodeling compared with the other two strains.

Conclusion: There were significant differences in the severity of peri-implantitis among the different mouse strains, suggesting that the genetic framework can affect implant survival and success. Future work is needed to dissect the genetic contribution to the development of peri-implantitis.

Keywords: bone loss; dental implant; genetics; murine.

Figure 1. Clinical and radiographical implant assessment at one and four weeks

(A) Representative clinical images of control (no ligature) and experimental (ligature) groups one and four weeks after ligature placement. 20X magnification. (B) Representative sagittal micro-computed tomography (micro-CT) images of control (no ligature) and experimental (ligature) C3H/HeJ, A/J, and C57BL/6J mouse groups four weeks after ligature placement. Notice the reduced alveolar bone in the experimental groups compared to control. (C) Representative axial micro-CT images of control (no ligature) and experimental (ligature) C3H/HeJ, A/J, and C57BL/6J mouse groups four weeks after ligature placement. Notice the circumferential bone loss around the implants. (D) Graph representing the averaged volumetric bone loss from the implant head to the alveolar bone one week after ligature placement. Data are mean ± standard error of the mean. ***p<0.001, **p<0.01, *p<0.05 (n≥5 for all groups). (E) Graph representing the averaged volumetric bone loss from the implant head to the alveolar bone four weeks after ligature placement. Data are mean ± standard error of the mean. ***p<0.001, **p<0.01, *p<0.05 (n≥5 for all groups).

Figure 2. Histological evaluation one week after ligature placement

(A) Representative hematoxylin and eosin (H&E) stained sagittal sections of control (no ligature) and experimental (ligature) groups. Note the increased soft tissue edema in experimental groups. 4X magnification. (B) 20X magnification of the area corresponding to the black square in (A). Note the increased alveolar bone porosity in ligature treated groups.

Figure 3. Collagen composition one week after ligature placement

(A) Representative bright field and picrosirius red stained sagittal sections of control (no ligature) and experimental (ligature) groups. 10X magnification. (B) 20X magnification of the area corresponding to the white square in (A).

Figure 4. Early assessment in neutrophil and osteoclast numbers

(A) NIMP-R14 immunohistochemistry, neutrophil staining, in alveolar bone and infiltrated connective tissue adjacent to the implant sites. Implants were removed before embedding the decalcified specimens. 20X magnification. (B) TRAP staining, osteoclastic cells (C) Graph representing the averaged number of osteoclasts in C3H/HeJ, A/J, and C57BL/6J control (no ligature) and experimental (ligature) groups. Data are mean ± standard error of the mean. ***p<0.001, **p<0.01, *p<0.05 (n≥3 for all groups).

Figure 5. Late Histological Changes in bone-implant interface

Histology of bone-implant interfaces in ground, undecalcified sections at four weeks after ligature placement by toluidine blue stain and calcein labeling (green fluorescence, FITC). 10X magnification. Note increased green fluorescence in the C57BL/6J experimental (ligature) group as compared to C3H/HeJ and A/J.

Appendix Figure 1

Histological evaluation four weeks after ligature placement. (A) Representative H&E stained sections of control (no ligature) and experimental (ligature) groups. 4X magnification. (B) 20X magnification of the area corresponding to the black square in (A).

Appendix Figure 2

Collagen composition four weeks after ligature placement. (A) Representative bright field and picrosirius red stained sagittal sections of control (no ligature) and experimental (ligature) groups. 10X magnification. (B) 20X magnification of the area corresponding to the black square in (A).