title: Type 2 diabetes impairs tendon repair after injury in a rat model.
abstract: Type 2 diabetes adversely affects the properties of native connective tissue. The underlying mechanisms, however, by which diabetes alters connective tissue metabolism, especially tendon, are poorly defined. The aim of this study was to determine the effect of type 2 diabetes on the mechanical, histological, and molecular properties of the intact and healing Achilles tendon. The right Achilles tendon was transected in 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats, while the left Achilles tendon was left intact. At 2 wk postinjury the intact and injured tendons were assessed by biomechanical testing and histology. The gene expression of collagen I and III, biglycan, versican, MMP-13, and MMP-3 was measured by quantitative RT-PCR, and their protein distribution was studied by immunohistochemistry. Intact tendons exhibited only small differences between the groups. In injured tendons, however, a significantly smaller transverse area and lower stiffness was found in diabetic GK compared with Wistar control rats. This correlated with impaired structural organization of collagen fibers and a reduced expression of collagen I and III in the injured tendons of the diabetic GK compared with Wistar control. Moreover, MMP-3 gene expression was downregulated in the injured diabetic GK tendons compared with injured Wistar controls. Our results indicate that in a rat model of diabetes tendon healing is impaired mainly due to altered expression of collagen and MMPs reflecting decreased degradation of matrix proteins and impaired tissue remodeling. Further our data suggest that therapeutic modulation of collagens or MMPs might be targets for new regenerative approaches in operated, injured, or maybe also degenerative tendon diseases in diabetes.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Aisha S
authors.initials: AS
authors.lastname: Ahmed
authors.forename: Nikos
authors.initials: N
authors.lastname: Schizas
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Mahmood
authors.initials: M
authors.lastname: Ahmed
authors.forename: C-G
authors.initials: CG
authors.lastname: Östenson
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 / Q000473:pathology; D000818:Animals; D058578:Biglycan / Q000235:genetics / Q000378:metabolism; D001696:Biomechanical Phenomena; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004548:Elasticity; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012421:Rupture; D013708:Tendon Injuries / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D053675:Versicans / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
chemical_list: C546886:Bgn protein, rat; D058578:Biglycan; D024042:Collagen Type I; D024061:Collagen Type III; C508324:Vcan protein, rat; D053675:Versicans; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D019278:Matrix Metalloproteinase 3