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高糖对肌腱衍生干细胞的影响:糖尿病肌腱疾病发病机制的启示

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

作者信息

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

机构信息

Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

出版信息

Oncotarget. 2017 Mar 14;8(11):17518-17528. 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.

摘要

糖尿病患者极易患上多种肌肉骨骼疾病,如肌腱病、肌腱断裂和肌腱愈合受损。然而,这些肌腱疾病的发病机制仍不清楚。在本研究中,我们旨在探讨高糖对体外培养的肌腱来源干细胞(TDSCs)的细胞增殖、细胞凋亡及肌腱相关标志物表达的影响。这些发现可能为糖尿病肌腱疾病的发病机制提供新的见解。通过MTT法和Annexin V-FITC/PI染色法评估不同组TDSCs的细胞增殖能力和凋亡率。通过qRT-PCR检测肌腱相关标志物(Scleraxis和胶原蛋白Iα1链)的mRNA表达。通过蛋白质印迹法检测肌腱相关标志物(肌腱调节蛋白和胶原蛋白I)的蛋白表达。用高糖(15mM和25mM)处理的TDSCs在第1天、第3天和第5天的增殖能力显著下降。当TDSCs在体外与高糖培养48小时时,其细胞凋亡显著增加。当用高糖处理24小时和48小时时,TDSCs中Scleraxis和胶原蛋白Iα1链的基因表达显著下降。当用高糖处理24小时和48小时时,TDSCs中肌腱调节蛋白和胶原蛋白I的蛋白表达显著下降。高糖可抑制体外培养的TDSCs的细胞增殖,诱导细胞凋亡并抑制其肌腱相关标志物的表达。这些发现可能解释了糖尿病肌腱疾病发病机制的一些病理机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3644/5392267/38710a624a0f/oncotarget-08-17518-g001.jpg

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