The effects of high glucose on tendon-derived stem cells: implications of the pathogenesis of diabetic tendon disorders.

Yu-Cheng Lin,Chen Wang,Hong-Liang Xu,Yun-Feng Rui,Song Zhao,Guang-Chun Dai,Gang Li,Gao-Jun Teng,Hui Chen,Ming Ni,Ying-Juan Li,Liu Shi

doi:10.18632/oncotarget.15418

Abstract

Patients with diabetes are at great risk to suffer many musculoskeletal disorders, such as tendinopathy, tendon rupture and impaired tendon healing. However, the pathogenesis of these tendon disorders still remains unclear. In this study, we aimed to investigate the effects of high glucose on cell proliferation, cell apoptosis and tendon-related markers expression of tendon-derived stem cells (TDSCs) in vitro. These findings might provide new insights into the pathogenesis of diabetic tendon disorders. The cell proliferative ability and apoptosis rate of TDSCs in different groups were evaluated by MTT assay and Annexin V-FITC/PI staining assay. The mRNA expression of tendon-related markers (Scleraxis and Collagen I alpha 1 chain) were assessed by qRT-PCR. The protein expression of tendon-related markers (Tenomodulin and Collagen I) were measured by Western blotting. The proliferative ability of TDSCs treated with high glucose (15mM and 25mM) decreased significantly at day1, day3 and day5. The cell apoptosis of TDSCs increased significantly when they were cultured with high glucose for 48h in vitro. The gene expression of Scleraxis and Collagen I alpha 1 chain in TDSCs decreased significantly when they were treated with high glucose for 24h and 48h. The protein expression of Tenomodulin and Collagen I in TDSCs decreased significantly when they were treated with high glucose for 24h and 48h. High glucose could inhibit cell proliferation, induce cell apoptosis and suppress the tendon-related markers expression of TDSCs in vitro. These findings might account for some pathological mechanisms underlying the pathogenesis of diabetic tendon disorders.

Highlights

Patients with diabetes, both type 1 and type 2 are at greater risk to suffer many musculoskeletal disorders, such as tendinopathy, limited joint mobility, tendon ruptures, adhesive capsulitis and impaired tendon healing ability than non-diabetic patients [1,2,3,4,5,6]
Cell morphology of tendon-derived stem cells (TDSCs) was slightly changed when they were treated with high glucose concentration for 24h
The results showed the significant differences between high glucose groups (15 and 25 mM) and normal glucose group (5.5mM), which implied that high glucose could inhibit TDSCs proliferation in vitro

Summary

Introduction

Both type 1 and type 2 are at greater risk to suffer many musculoskeletal disorders, such as tendinopathy, limited joint mobility, tendon ruptures, adhesive capsulitis and impaired tendon healing ability than non-diabetic patients [1,2,3,4,5,6]. A strong evidence has been reported that diabetes is associated with higher risk of tendinopathy [5]. Diabetic patients have a greater risk of tendinopathy and/or traumatic rupture in musculoskeletal tissues because of the altered structural properties in tendon [7]. For the impaired Achilles tendons, patients with diabetes have higher proportion of postoperative infection and weaker tendon healing ability [6]. The underlying cellular and molecular mechanisms of the pathogenesis of diabetic tendon disorders are still unknown

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