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. 2017 Mar 14;8(11):17518-17528.
doi: 10.18632/oncotarget.15418.

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

Yu-Cheng Lin  1 , Ying-Juan Li  2 , Yun-Feng Rui  1   3   4 , Guang-Chun Dai  1 , Liu Shi  1   5   6 , Hong-Liang Xu  3 , Ming Ni  7 , Song Zhao  1 , Hui Chen  1 , Chen Wang  1 , Gang Li  5   6 , Gao-Jun Teng  8
Affiliations
Free PMC article

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

Yu-Cheng Lin et al. Oncotarget. .
Free PMC article

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.

Keywords: Pathology Section; diabetic tendon disorders; high glucose; pathogenesis; tendon-derived stem cells.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that there is no conflict of interest regarding the publication of this manuscript.

Figures

Figure 1
Figure 1. MTT assay
Treatment of TDSCs with high glucose (15mM and 25mM) decreased cell proliferation at day1, day3 and day5. *P ≤ 0.05.
Figure 2
Figure 2. Apoptosis assay
A., B., C.. 24h after 5.5mM, 15mM, 25mM glucose induction separately; D., E., F.. 48h after 5.5mM, 15mM, 25mM glucose induction separately; G. Statistical results in 24h; H. Statistical results in 48h.There was no statistical difference between high glucose groups (15 and 25 mM) and normal glucose group (5.5mM) after 24 hours culture, however, significant differences were observed between high glucose groups and normal glucose group at 48 hours. *P ≤ 0.05.
Figure 3
Figure 3. qRT-PCR assay----Col1a1
A. 24h after glucose induction; B. 48h after glucose induction; The mRNA expression of Col1a1 was down-regulated when TDSCs were treated with high glucose (15mM and 25mM) at 24 hours and 48 hours, compared with that in normal glucose group (5.5mM). *P ≤ 0.05 .
Figure 4
Figure 4. qRT-PCR assay----Scx
A. 24h after glucose induction; B. 48h after glucose induction; The mRNA expression of Scx was down-regulated when TDSCs were treated with high glucose (15mM and 25mM) at 24 hours and 48 hours, compared with that in normal glucose group (5.5mM). *P ≤ 0.05.
Figure 5
Figure 5. Western blotting assay
The expression of tendon-related proteins (Tnmd and Col-1).
Figure 6
Figure 6. Western blotting ----Tnmd
A. 24h after glucose induction; B. 48h after glucose induction; The protein expression of Tnmd was decreased in treatment with high glucose concentrations (15mM and 25mM) at 24 hours and 48 hours, compared with treatment with 5.5 mM glucose concentration. *P ≤ 0.05.
Figure 7
Figure 7. Western blotting ---- Col-1
A. 24h after glucose induction; B. 48h after glucose induction; The protein expression of Col-1 was decreased after the high glucose treatment (15mM and 25mM) for 24 hours and 48 hours compared with that in 5.5mM glucose group. *P ≤ 0.05.
Figure 8
Figure 8. Hypothetical model of pathogenesis of diabetic tendon disorders
See this image and copyright information in PMC

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References

    1. Cagliero E, Apruzzese W, Perlmutter GS, Nathan DM. Musculoskeletal disorders of the hand and shoulder in patients with diabetes mellitus. Am J Med. 2002;112:487–90. - PubMed
    1. Rosenbloom AL, Silverstein JH. Connective tissue and joint disease in diabetes mellitus. Endocrinol Metab Clin North Am. 1996;25:473–83. - PubMed
    1. Sukenik S, Weitzman S, Buskila D, Eyal A, Gross J, Horowitz J. Limited joint mobility and other rheumatological manifestations in diabetic patients. Diabete Metab. 1987;13:187–92. - PubMed
    1. Bedi A, Fox AJ, Harris PE, Deng XH, Ying L, Warren RF, Rodeo SA. Diabetes mellitus impairs tendon-bone healing after rotator cuff repair. J Shoulder Elbow Surg. 2010;19:978–88. doi: 10.1016/j.jse.2009.11.045. - DOI - PMC - PubMed
    1. Ranger TA, Wong AM, Cook JL, Gaida JE. Is there an association between tendinopathy and diabetes mellitus? A systematic review with meta-analysis. Br J Sports Med. 2015 doi: 10.1136/bjsports-2015-094735. - DOI - PubMed