Pioglitazone Antagonized the Effects of Advanced Glycation End Products on Achilles Tendon Healing and Improved the Recovery of Tendon Biomechanical Properties.

ABSTRACT

Purpose: Advanced glycation end products (AGEs) often accumulate in the Achilles tendon during the course of diabetes. This study aims to determine the impact of AGEs on tendon repair and explore the role of pioglitazone in mitigating this impact. Methods: Forty-eight male 8 week-old Sprague Dawley rats were selected in this study. After transection of Achilles tendon, the rats were randomly divided into four groups. The Achilles tendons of rats were injected with 1000 mmol/L D-ribose to elevate the content of AGEs within the tendons in two groups, the remaining two groups received injections of phosphate buffered saline (PBS) solution. Subsequently, the first two groups were respectively received oral administration of pioglitazone (20 mg/kg/day) and PBS. The remaining two groups were given the same treatment. The expression of the collagen-I, TNF-α, IL-6 of the repaired tendon were detected. The macroscopic, pathologic and biomechanical aspects of tendon healing were also evaluated. Results: AGEs accumulation in tendon during the healing process increases the expression of inflammatory factors such as TNF-α and IL-6, leading to insufficient synthesis of collagen-I and delayed recovery of the tendon's tensile strength. Pioglitazone significantly attenuated the damage caused by AGEs to the tendon healing process, effectively improving the recovery of tendon tensile strength. Pioglitazone could not inhibit the generation of AGEs in the tissue and also had no impact on the normal healing process of the tendon. Conclusions: Pioglitazone could prevent the deleterious impact of AGEs on the Achilles tendon healing and improve the biomechanical properties of the tendon.