Evaluating the role of type 2 diabetes mellitus in rotator cuff tendinopathy: Development and analysis of a novel rat model

Abstract

ObjectiveTo establish and validate an intact rotator cuff rat model for exploring the pathophysiological effects of type 2 diabetes on the rotator cuff tendon in vivo.MethodsA total of 45 adult male rats were randomly divided into a control group (n = 9) and type 2 diabetes group (n=36). The rats were sacrificed at 2 weeks (T2DM-2w group, n=9), 4 weeks (T2DM-4w group, n=9), 8 weeks (T2DM-8w group, n=9), and 12 weeks (T2DM-12w group, n=9) after successful modeling of type 2 diabetes. Bilateral shoulder samples were collected for gross observation and measurement, protein expression(enzyme-linked immunosorbent assay,ELISA), histological evaluation, biomechanical testing, and gene expression (real-time quantitative polymerase chain reaction, qRT-PCR).ResultsProtein expression showed that the expression of IL-6 and Advanced glycation end products (AGEs)in serum increased in type 2 diabetic group compared with the non-diabetic group. Histologically, collagen fibers in rotator cuff tendons of type 2 diabetic rats were disorganized, ruptured, and with scar hyperplasia, neovascularization, and extracellular matrix disturbances, while Bonar score showed significant and continuously aggravated tendinopathy over 12 weeks. The biomechanical evaluation showed that the ultimate load of rotator cuff tendons in type 2 diabetic rats gradually decreased, and the ultimate load was negatively correlated with AGEs content. Gene expression analysis showed increased expression of genes associated with matrix remodeling (COL-1A1), tendon development (TNC), and fatty infiltration (FABP4) in tendon specimens from the type 2 diabetic group.ConclusionPersistent type 2 diabetes is associated with the rupture of collagen fiber structure, disturbance in the extracellular matrix, and biomechanical decline of the rotator cuff tendon. The establishment of this new rat model of rotator cuff tendinopathy provides a valuable research basis for studying the cellular and molecular mechanisms of diabetes-induced rotator cuff tendinopathy.

Untargeted metabolomics reveals dynamic changes in metabolic profiles of rat supraspinatus tendon at three different time points after diabetes induction

“…Some studies have shown that diabetes alters the physical and chemical properties of tendons and the arrangement of collagen fibers, extracellular matrix composition, and biomechanics in a high-glucose microenvironment ( 5 ). The current study demonstrated that the degree of tendinopathy gradually worsens and the biomechanical properties decrease in the supraspinatus tendon of rats at 2, 4, 8, and 12 weeks after diabetes induction ( 6 ). However, studies on how diabetes leads to the continuous progression and deterioration of rotator cuff tendinopathy have not been reported; also, the changes in endogenous small molecules and the involved biological pathways with the progression of diabetes remain unclear.…”

Diabetes mellitus as a risk factor for postoperative complications following arthroscopic rotator cuff repair

“… 26 The chronic hyperglycemia observed in diabetes is responsible for increased advanced glycosylation end products (AGEs); accumulation of AGEs within joints can cause the load-bearing collagen proteins found in tendons and ligaments to crosslink, manifesting in biomechanical disturbance. 29 Furthermore, the association of AGEs with their endothelial receptor produces oxidative stress and the release of inflammatory cytokines, increasing vessel stiffness and permeability. 6 This aggravates the vascular environment seen in diabetes, leading to the disproportionate expression of type III collagen in tenocytes, causing greater weakness to force and susceptibility to rupture.…”

Metabolic Syndrome and Tendon Disease: A Comprehensive Review

“…The supraspinatus tendon of SD mice fed a high-fat diet showed sparse arrangement and microtears of collagen fibers at 2 weeks, and significant tearing and infiltration of inflammatory cells in tendon collagen fibers at 12 weeks. 112 By integrating the advantages and disadvantages of both monogenic animal models and DIO animal models, the selection of an appropriate animal model during experimental processes can further reflect the impact of MS on tendons.…”