Laboratory Research
We have previously shown that the genetic knockout of the cysteine protease cathepsin K facilitates the healing of wounds in diabetic mice. Therefore, the objective of this study was to assess the efficacy of odanacatib, a small molecule inhibitor of cathepsin K to accelerate diabetic wound healing in a clinically relevant porcine model.
Methods:
Eight female Yorkshire pigs (3-months-old) were rendered diabetic by streptozocin (150 mg/Kg/iv). Four weeks following the induction of diabetes, ten full-thickness excision wounds were created on the backs of the pigs. Individual wounds were treated intradermally with odanacatib (300 or 10 ng/wound), PBS, or becaplermin (Regranex®, 100 ug/g; 0.6 inch/wound) on days 0, 7, and 14 post-wounding. Wounds were photographed for wound area measurement. Histological sections were stained with H&E, Mason’s trichome, CD45, and CD31. Statistical analysis was performed using an ANOVA followed by Tukey’s post hoc test, and a p-value ≤ 0.05 was considered statistically significant.
Results:
Our data showed the average day to healing for the wounds for the control (non-diabetic vehicle-treated animals) was 25.5 ± 1.0 days, while the wounds of the diabetic animals healed at 30.2 ± 2.4 days (mean ± SEM, n=4-5 wounds). In contrast, full closure of the becaplermin-treated diabetic wounds averaged 32.8 ± 1.2 days (n=4). Wounds treated with the higher dose of odanacatib exhibited accelerated healing, at rates similar to that of the vehicle-treated wounds, exhibiting a full closure at 25.4 ± 1.5 days. The lower dose of odanacatib did not alter the rate of wound healing in diabetic pigs.
Discussion: Our results demonstrate that odanacatib accelerates wound healing in diabetic pigs, suggesting its potential clinical utility.
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