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.
Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.
Objective This cross-sectional study was aimed to update the assessment of prevalence, characteristics, and risk factors of the elderly with hip fractures in a non-institutionalized American population. Methods This current study included a total of 31,034 participants from the existing National Health and Nutritional Examination Survey (NHANES) database from 2005 to 2010, and 4,265 participants aged 65 years and older were ultimately identified. Their condition of hip fractures was determined by method of questionnaires according to the orthopedic surgeons’ diagnosis, and related epidemiological and demographic data were further collected. The univariate analysis was used to screen the risk factors of hip fractures in the elderly, and the logistic regression model was established to conduct the multivariate analysis. Results Of the total 4,265 participants with clear information of hip fractures in elderly, 127 individuals with hip fractures were identified according to results of questionnaires, exhibiting a prevalence of 28.49 per 1,000 (95% confidence interval [CI]=21.38–35.60) for males and 31.03 per 1,000 (95% CI=23.72–38.35) for females. The mean age of the elderly with hip fractures was 77.12±5.88 years and tumble (48.0%) was the primary factor. In univariate analysis, age, race, smoking, drinking alcohol, and combined with osteoporosis were regarded as risk factors. Multivariate analysis showed that age (80 years and older), living alone, smoking, combined with diabetes and osteoporosis were the independent risk factors. Conclusion Our nationwide data indicate the prevalence of hip fractures in the elderly is generally on the rise, and the female occupies a higher proportion. Age (especially aged 80 years and older), race (mainly Non-Hispanic white), smoking, drinking alcohol, living alone, combined with diabetes and osteoporosis may be closely linked to the occurrence of hip fractures in the elderly, although these variables still need to be verified in further prospective investigations.
Osteoporosis (OP) is a kind of systemic metabolic disease characterized by the decreased bone mass and destruction of bone microstructure. In recent years, it has become an expectant research trend...
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.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1108-6) contains supplementary material, which is available to authorized users.
The link between tendon stem/progenitor cells (TSPCs) senescence and tendon aging has been well recognized. However, the cellular and molecular mechanisms of TSPCs senescence are still not fully understood. In present study, we investigated the role of Aquaporin 1 (AQP1) in TSPCs senescence. We showed that AQP1 expression declines with age during tendon aging. In aged TSPCs, overexpression of AQP1 significantly attenuated TSPCs senescence. In addition, AQP1 overexpression also restored the age-related dysfunction of self-renewal, migration and tenogenic differentiation. Furthermore, we demonstrated that the JAK-STAT signaling pathway is activated in aged TSPCs, and AQP1 overexpression inhibited the JAK-STAT signaling pathway activation which indicated that AQP1 attenuates senescence and age-related dysfunction of TSPCs through the repression of JAK−STAT signaling pathway. Taken together, our findings demonstrated the critical role of AQP1 in the regulation of TSPCs senescence and provided a novel target for antagonizing tendon aging.
Diminished regeneration or healing capacity of tendon occurs during aging. It has been well demonstrated that tendon stem/progenitor cells (TSPCs) play a vital role in tendon maintenance and repair. Here, we identified an accumulation of senescent TSPCs in tendon tissue with aging. In aged TSPCs, the activity of JAK-STAT signaling pathway was increased. Besides, genetic knockdown of JAK2 or STAT3 significantly attenuated TSPC senescence in aged TSPCs. Pharmacological inhibition of JAK-STAT signaling pathway with AG490 similarly attenuated cellular senescence and senescence-associated secretory phenotype (SASP) of aged TSPCs. In addition, inhibition of JAK-STAT signaling pathway also restored the age-related dysfunctions of TSPCs, including self-renewal, migration, actin dynamics, and stemness. Together, our findings reveal the critical role of JAK-STAT signaling pathway in the regulation of TSPC aging and suggest an ideal therapeutic target for the age-related tendon disorders.
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