Expressional changes in growth and inflammatory mediators during Achilles tendon repair in diabetic rats: new insights into a possible basis for compromised healing

Abstract

Dysregulation of growth and inflammatory mediators might contribute to defective tissue homeostasis and healing, as commonly observed in sedentary lifestyles and in conditions such as diabetes mellitus type-2. The present study aims to assess expression changes in growth and inflammatory mediators in the intact and healing Achilles tendon of type-2 diabetic rats. The study utilized 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats. The right Achilles tendon was transected in all animals, whereas the left Achilles tendon remained intact. At 2 weeks post-injury, intact and injured tendons were assessed for gene expression for VEGF, Tβ-4, TGF-β1, IGF-1, COX-2, iNOS, HIF-1α, and IL-1β by quantitative reverse transcription plus the polymerase chain reaction, and their protein distribution was studied by immunolocalization. In injured tendons of diabetic GK rats, VEGF and Tβ-4 mRNA and corresponding protein levels were significantly down-regulated compared with those of injured Wistar controls. Compared with intact tendons of diabetic GK rats, TGF-β1, IGF-1, and COX-2 RNA levels were higher, whereas iNOS mRNA levels were lower in injured tendons of diabetic GK rats. Within Wistar controls, healing at 2 weeks post-injury led to significantly down-regulated VEGF and iNOS mRNA levels in injured tendons, whereas TGF-β1 and HIF-1α mRNA levels increased compared with intact tendons. Thus, dysregulation of inflammatory and growth mediators occurs in type-2 diabetes injured tendons. Our data suggest that therapeutic modulation of Tβ-4 and VEGF represent a new regenerative approach in operated, injured, or degenerative tendon diseases in diabetes.