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重组人脂联素作为一种治疗糖尿病性腱病的潜在蛋白,可促进体外肌腱细胞祖细胞的增殖和肌腱形成分化。

Recombinant human adiponectin as a potential protein for treating diabetic tendinopathy promotes tenocyte progenitor cells proliferation and tenogenic differentiation in vitro.

机构信息

1. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Int J Med Sci. 2013 Nov 27;10(13):1899-906. doi: 10.7150/ijms.6774. eCollection 2013.

Abstract

Adiponectin is an adipocyte-secreting hormone that increases cell sensitivity to insulin. It has been previously demonstrated that this hormone protects against Type II Diabetes and, is found to concurrently promote cell proliferation and differentiation. It is postulated that diabetic patients who suffer from tendinopathy may benefit from using adiponectin, which not only improves the metabolism of diabetic ridden tenocytes but also promotes progenitor cell proliferation and differentiation in tendons. These changes may result in tendon regeneration, which, in diabetic tendinopathy, is difficult to treat. Considering that such findings have yet to be demonstrated, a study was thus conducted using diabetic ridden human tenocyte progenitor cells (TPC) exposed to recombinant adiponectin in vitro. TPC were isolated from tendons of diabetic patients and exposed to 10 μg/ml adiponectin. Cell proliferation rate was investigated at various time points whilst qPCR were used to determine the tenogenic differentiation potential. The results showed that adiponectin significantly reduced blood glucose in animal models. The proliferation rate of adiponectin-treated TPCs was significantly higher at 6, 8 and 10 days as compared to untreated cells (p<0.05). The levels of tenogenic genes expression (collagen I, III, tenomodulin and scleraxis) were also significantly upregulated; whilst the osteogenic (Runx2), chondrogenic (Sox9) and adipogenic (PPARУγ) gene expressions remained unaltered. The results of this study suggest that adiponectin is a potential promoter that not only improves diabetic conditions, but also increases tendon progenitor cell proliferation and differentiation. These features supports the notion that adiponectin may be potentially beneficial in treating diabetic tendinopathy.

摘要

脂联素是一种脂肪细胞分泌的激素,可增加细胞对胰岛素的敏感性。先前已经证明,这种激素可以预防 2 型糖尿病,并且同时发现它可以促进细胞增殖和分化。据推测,患有肌腱病的糖尿病患者可能受益于使用脂联素,它不仅改善了糖尿病 ridden 肌腱细胞的新陈代谢,而且促进了肌腱中祖细胞的增殖和分化。这些变化可能导致肌腱再生,在糖尿病性肌腱病中,这是很难治疗的。考虑到这些发现尚未得到证实,因此进行了一项研究,使用在体外暴露于重组脂联素的糖尿病 ridden 人肌腱细胞祖细胞(TPC)。TPC 从糖尿病患者的肌腱中分离出来,并暴露于 10 μg/ml 的脂联素中。在不同时间点研究细胞增殖率,同时使用 qPCR 来确定肌腱分化潜力。结果表明,脂联素可显著降低动物模型中的血糖水平。与未处理的细胞相比,脂联素处理的 TPC 在 6、8 和 10 天时的增殖率明显更高(p<0.05)。肌腱生成基因表达(I 型、III 型胶原、肌腱调蛋白和 Scleraxis)的水平也明显上调;而成骨基因(Runx2)、软骨基因(Sox9)和脂肪基因(PPARγ)的表达保持不变。这项研究的结果表明,脂联素是一种潜在的促进剂,不仅可以改善糖尿病状况,还可以增加肌腱祖细胞的增殖和分化。这些特征支持这样一种观点,即脂联素可能在治疗糖尿病性肌腱病方面具有潜在的益处。

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