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Open Access 01-12-2024 | Research

Investigating the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus in rats using untargeted metabolomics analysis

Authors: Kuishuai Xu, Liang Zhang, Tianrui Wang, Tengbo Yu, Xia Zhao, Ning Yu, Yingze Zhang

Published in: BMC Musculoskeletal Disorders | Issue 1/2024

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Abstract

Objective

To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis.

Methods

The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed.

Results

With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs (P < 0.01) were mainly associated with the pathways of galactose metabolism, which could be involved in the development of diabetes-induced supraspinatus tendinopathy.

Conclusion

T2DM causes tendinopathy of the supraspinatus muscle in rats. 10 key DEMs obtained by untargeted metabolomics assay suggested that the development of diabetes-induced supraspinatus tendinopathy was associated with changes in metabolic pathways, such as galactose metabolism. melezitose and raffinose hold promise as a biomarker for disease discrimination and/or disease indication in diabetic supraspinatus tendinopathy.
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Metadata
Title
Investigating the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus in rats using untargeted metabolomics analysis
Authors
Kuishuai Xu
Liang Zhang
Tianrui Wang
Tengbo Yu
Xia Zhao
Ning Yu
Yingze Zhang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2024
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-024-08061-1