Mechanisms linking periodontitis and diabetes

Background + Aims

• Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in detecting DNA damage and co-ordinating repair. Excessive activation can promote inflammation and deplete cellular energy; diabetes may amplify this process through nitrosative stress (damage caused by excessive reactive nitrogen compounds such as peroxynitrite).
• This study aimed to:
  • Determine whether PARP activation contributes to diabetes-aggravated periodontitis and whether inhibiting this enzyme reduces periodontal inflammation and bone destruction.

Materials + Methods

• The study used 48 male Sprague–Dawley rats, with diabetes induced in half using streptozotocin, which damages insulin-producing pancreatic cells.
• 2-weeks later, periodontitis was induced by placing a nylon ligature around one upper second molar. The corresponding tooth on the opposite side remained unligated as a control.
• Half of the diabetic and non-diabetic rats received the PARP inhibitor 1,5-isoquinolinediol, administered by daily injection at 3 mg/kg for 2-weeks, starting when the ligature was placed.
• Gingival PARP activity was assessed by staining for poly(ADP-ribose), the product formed when PARP is activated.
• Researchers measured inflammatory cell infiltration, inflammatory gene expression and nitrotyrosine, a marker of nitrosative stress.
• Micro-CT imaging assessed alveolar bone loss. Blood glucose, HbA1c, body weight and circulating white blood cells were also measured.

Results

• Diabetes and periodontitis each increased gingival PARP activity.
• Diabetic rats with periodontitis had approximately:
  • 1.5 times as many PARP-active cells as non-diabetic rats with periodontitis.
  • 1.5 times as many gingival monocytes/macrophages (immune cells involved in inflammatory responses)
• PARP inhibition:
  • Reduced monocyte/macrophage infiltration in both diabetic and non-diabetic rats with periodontitis.
  • Suppressed elevated expression of TNF-α (an inflammatory signalling protein) and iNOS (an enzyme that produces nitric oxide) in the diabetic periodontal tissues,
  • Reduced nitrotyrosine-positive gingival cells by approximately 56% in diabetic rats with periodontitis.
• Untreated diabetic rats had greater measured bone loss than non-diabetic rats with periodontitis (1.19 versus 0.88 mm). PARP inhibition reduced the bone-loss measure by approximately 32% in diabetic rats and 24% in non-diabetic rats.
• Blood glucose and HbA1c were not significantly altered, suggesting that the periodontal benefits were not explained by improved glycaemic control.

Limitations