A Novel Diabetic Arthritic Model in Rats Induced by Streptozotocin, High-Fat Diet, and Complete Freund's Adjuvant.

Abstract

Ankle arthrodesis is one of the treatments of choice, particularly in late-stage and unstable diabetic Charcot arthropathy. Unfortunately, poor healing capacity might play a role in the high nonunion rate (10-40%). The advancement in regenerative medicine opens a new horizon for enhancing fusion after ankle arthrodesis in patients with poor healing capacity. However, a suitable small animal model is warranted to study the effectivity of these regenerative medicine approaches. Streptozotocin (STZ)-induced diabetes models and adjuvant-induced arthritis models with complete Freund's adjuvant are two established models. However, no study has combined those two models to make a diabetic arthritic model that more closely resembles the condition in Charcot arthropathy. Twenty male Sprague-Dawley rats were assigned into five groups, consisting of one control group, and four diabetic groups which were induced by STZ injection and a high-fat diet. Among these diabetic rats, two groups received complete Freund's adjuvant (CFA) injections to the left ankle of the hind limb. The control group, one of the diabetic-only groups, and one of the arthritic-diabetic-induced groups were euthanized at 4 weeks after STZ induction, and the remainder were euthanized 6 weeks after STZ induction. Clinical, radiological, and histological examinations were then compared in all five groups. Diabetic status was successfully achieved in the model, which was maintained until the completion of the study. The CFA-induced ankles were significantly larger than the contralateral ankles in all groups (p<0.05). Histopathological evaluation confirmed arthritic changes in the CFA-induced group with less variability after 4 weeks of arthritis induction. This rat model of arthritic diabetic mimics the progressive and chronic nature of Charcot arthropathy in humans. This model can be further use to study treatments that might enhance the fusion rate in ankle arthrodesis in healing-defective patients such as those with diabetes. 5.