Impaired dental implant osseointegration in rat with streptozotocin-induced diabetes

J Periodontal Res. 2022 Apr;57(2):412-424. doi: 10.1111/jre.12972. Epub 2022 Jan 17.

Abstract

Objective: Few studies have reported on the impact of oxidative stress on the dental implant failure. The aim of this study was to investigate the impact of hyperglycemia-induced oxidative stress on dental implant osseointegration in diabetes mellitus (DM).

Methods: Acid-treated titanium implants were bilaterally placed in the maxillary alveolar ridge of streptozotocin-induced diabetic (DM group) and control rats after extraction of first molars. Histological analysis and micro-push-out test were performed 4 weeks after surgery. Oxidative stress and osteogenic markers in the surrounding bone were quantified by real-time polymerase chain reaction. In the in vitro study, rat bone marrow-derived mesenchymal stem cells (BMMSCs) were cultured on acid-treated titanium discs in a high-glucose (HG) or normal environment. Intracellular reactive oxygen species (ROS), cell proliferation, alkaline phosphatase (ALP) activity, and extracellular calcification were evaluated following antioxidant treatment with N-acetyl-L-cysteine (NAC).

Results: The implant survival rate was 92.9% and 75.0% in control and DM group, respectively. Bone-implant contact and push-out loads were significantly lower in the DM group. Expression of superoxide dismutase 1 at the mRNA level and on immunohistochemistry was significantly lower in the DM group. In vitro experiments revealed that the HG condition significantly increased ROS expression and suppressed the proliferation and extracellular calcification of BMMSCs, while NAC treatment significantly restored ROS expression, cell proliferation, and calcification. The ALP activity of both groups was not significantly different.

Conclusion: In diabetes, high-glucose-induced oxidative stress downregulates proliferation and calcification of BMMSCs, impairing osseointegration and leading to implant failure.

Keywords: acetylcysteine; diabetes mellitus; mesenchymal stem cells; osseointegration; oxidative stress; reactive oxygen species.

MeSH terms

  • Animals
  • Dental Implants*
  • Diabetes Mellitus, Experimental* / metabolism
  • Osseointegration
  • Osteogenesis
  • Rats
  • Streptozocin
  • Titanium / pharmacology

Substances

  • Dental Implants
  • Streptozocin
  • Titanium