Antioxidant effect of enamel matrix derivative for early phase of periodontal tissue regeneration in diabetes

J Periodontol. 2022 Aug;93(8):1206-1217. doi: 10.1002/JPER.21-0413. Epub 2022 Jan 28.

Abstract

Background: Diabetes involves metabolic disorders in various tissues via hyperglycemia-induced oxidative stress. This study aimed to investigate the antioxidative effect of enamel matrix derivative (EMD) on periodontal regeneration in diabetes.

Methods: Twenty-two rats were equally divided into streptozotocin (STZ)-induced diabetes or control group. Two months after induction of hyperglycemia, systemic oxidative stress was measured using urinary 8-hydroxy-2'-deoxyguanosine. EMD or saline was applied into the intrabony defects created in the bilateral maxillary molar. mRNA expressions of inflammatory and oxidative stress markers were quantified (n = 6). Histometric analyses and immunohistochemistry of superoxide dismutase-1 (SOD-1) were performed 7 days postoperatively (n = 5). For in vitro experiments, the bone marrow-derived mesenchymal stem cells were isolated from rat femur and cultured in a high glucose (HG) or control medium. Reactive oxygen species (ROS) measurement and alizarin red staining were performed with/without EMD.

Results: Systemic oxidative stress was significantly higher in the diabetic group. The connective tissue attachment and cementum formation were significantly increased at EMD-treated sites in both diabetic and non-diabetic groups. The expression of nicotinamide adenine dinucleotide phosphate oxidase two and four was significantly lower at EMD-treated sites than at EMD-untreated sites in both diabetic and non-diabetic rats. Immunohistochemistry showed significantly higher SOD-1 expression at the EMD-treated site. In vitro, HG culture had significantly higher ROS production compared with control, which was downregulated by EMD. EMD treatment significantly recovered the impaired calcification in HG.

Conclusion: EMD promoted early-phase wound healing and periodontal tissue regeneration in the surgically created bony defect of STZ-induced diabetic rat by suppressing hyperglycemia-induced oxidative stress.

Keywords: antioxidant; diabetes mellitus; oxidative stress; periodontal regeneration; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss* / surgery
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Dental Enamel Proteins* / pharmacology
  • Dental Enamel Proteins* / therapeutic use
  • Diabetes Mellitus, Experimental* / surgery
  • Guided Tissue Regeneration, Periodontal
  • Hyperglycemia* / drug therapy
  • Hyperglycemia* / surgery
  • Rats
  • Reactive Oxygen Species
  • Superoxide Dismutase / pharmacology
  • Wound Healing

Substances

  • Antioxidants
  • Dental Enamel Proteins
  • Reactive Oxygen Species
  • Superoxide Dismutase