title: 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.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, 17177, Stockholm, Sweden, aisha.ahmed@ki.se.
authors.forename: Aisha S
authors.initials: AS
authors.lastname: Ahmed
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Nicos
authors.initials: N
authors.lastname: Schizas
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ahmed
authors.forename: Claes-Goran
authors.initials: CG
authors.lastname: Ostenson
authors.forename: Paul
authors.initials: P
authors.lastname: Salo
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hewitt
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ackermann
mesh_terms: D000125:Achilles Tendon / Q000293:injuries* / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017208:Rats, Wistar; D014945:Wound Healing / Q000502:physiology*