Abstract
BackgroundPatients with diabetes mellitus (DM) often suffered with many musculoskeletal disorders, such as tendon rupture and tendinopathy. However, the understanding of the pathogenesis of these alternations is limited. This study was designed to investigate the role of tendon-derived stem cells (TDSCs) in histopathological alterations of DM tendons.MethodsForty-two SD rats were randomly and equally divided into a diabetes group (DG) and control group (CG). DM was induced by streptozotocin (65 mg/kg). The patellar tendons were isolated at weeks 1, 2, and 4 for histological analysis. TDSCs were isolated at week 2 for osteo-chondrogenic differentiation analysis. Mann-Whitney U test was used with SPSS. p < 0.050 was statistically significant.ResultsMicro-tears of collagen fibers and altered appearance of tendon cells were observed in DG tendons. DG tendons exhibited significantly higher expression of OPN, OCN, SOX9, and Col II and decreased expression of Col I and tenomodulin (TNMD) at week 2. Diabetic TDSCs (dTDSCs) demonstrated significantly decreased proliferation ability and increased osteogenic and chondrogenic differentiation ability. Osteo-chondrogenic markers BMP2, ALP, OPN, OCN, Col II, and SOX9 were also significantly increased while tenogenic markers Col I and TNMD were decreased in dTDSCs.ConclusionThese results suggested the erroneous differentiation of dTDSCs might account for the structural and non-tenogenic alternations in DM tendons, which provided new cues for the pathogenesis of tendon disorders in DM.
Highlights
Patients with diabetes mellitus (DM) often suffered with many musculoskeletal disorders, such as tendon rupture and tendinopathy
Taken together with the calcium deposition found in the Achilles tendons in DM patients [10], and such non-tenogenic changes in diabetic tendons have not been studied in depth, we raised the hypothesis that diabetic tendons have characteristics of structural and non-tenogenic changes as in classical tendinopathy, and the impaired function of tendon-derived stem cells (TDSCs) might account for these pathological changes, which might provide some implications for the cellular mechanism of the diabetic tendon disorders
The mean area under the curve (AUC) in intraperitoneal glucose tolerance test (IPGTT) of diabetes group (DG) subjects significantly increased when compared with the controls 3 days post-STZ injection (22,530 ± 2190 and 8956 ± 1126, respectively) (**p = 0.002), which provided a quantitative index of the severity of hyperglycemia in DG subjects (Table 2), indicating the sustained hyperglycemia of DG rats after STZ injected
Summary
Patients with diabetes mellitus (DM) often suffered with many musculoskeletal disorders, such as tendon rupture and tendinopathy. This study was designed to investigate the role of tendon-derived stem cells (TDSCs) in histopathological alterations of DM tendons. SHI et al Stem Cell Research & Therapy (2019) 10:27 decreased biomechanical properties of the DM tendons were reported [12,13,14,15]. We found tendon-derived stem cells (TDSCs) isolated from collagenase-induced tendinopathy rat model exhibited the increased osteo-chondrogenic differentiation potential and decreased tenogenic differentiation potential [17]. Taken together with the calcium deposition found in the Achilles tendons in DM patients [10], and such non-tenogenic changes in diabetic tendons have not been studied in depth, we raised the hypothesis that diabetic tendons have characteristics of structural and non-tenogenic changes as in classical tendinopathy, and the impaired function of TDSCs might account for these pathological changes, which might provide some implications for the cellular mechanism of the diabetic tendon disorders
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