组蛋白去乙酰化酶抑制剂可在高血糖条件下恢复牙髓干细胞的成牙分化潜能

Mahshid Hodjat, Fatemeh Farshad, Mahdi Gholami, Mohammad Abdollahi, Khandakar A S M Saadat
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摘要

目的:糖尿病引起的并发症可导致干细胞功能障碍,损害其向各种细胞系分化的能力。本研究评估了在高血糖条件下,组蛋白去乙酰化酶抑制剂丙戊酸和三环锡A对牙髓干细胞牙源性分化潜能的影响:方法:胰高血糖素(STZ)诱导12只雄性Wistar大鼠患糖尿病。使用微型计算机断层扫描检查牙齿参数。通过碱性磷酸酶测定、使用实时 PCR 检测牙本质基质蛋白 1 和牙本质纤溶蛋白的基因表达以及茜素红染色检测钙沉积,评估暴露于 30 mM 葡萄糖的人牙髓干细胞的成牙潜能:结果:与对照组相比,糖尿病大鼠的牙本质厚度和牙根长度均有所减少,同时还发现在分离的糖尿病牙髓组织中,组蛋白去乙酰化酶 3 和 2 的基因表达量显著增加。在高血糖条件下,培养的人牙髓干细胞中牙髓形成相关标志物的基因表达和碱性磷酸酶活性明显降低。加入丙戊酸和三氯他汀 A 后,牙本质分化标志物得以恢复,包括钙沉积、牙本质矽磷蛋白、牙本质基质蛋白 1 基因表达和碱性磷酸酶活性:数据表明,高血糖会对牙髓间充质干细胞的成牙潜能产生负面影响。然而,组蛋白去乙酰化酶抑制剂可改善受损的牙本质分化能力。这项研究表明,组蛋白去乙酰化酶可能是增强糖尿病患者牙髓细胞再生矿化的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Histone Deacetylase Inhibitors Restore the Odontogenic Differentiation Potential of Dental Pulp Stem Cells under Hyperglycemic Conditions.

Objective: Complications arising from diabetes can result in stem cell dysfunction, impairing their ability to undergo differentiation into various cellular lineages. The present study evaluated the effect of histone deacetylase inhibitors, Valproic acid and Trichostatin A, on the odontogenic differentiation potential of dental pulp stem cells under hyperglycemic conditions.

Methods: Streptozotocin (STZ) induced diabetes mellitus in 12 male Wistar rats. Dental parameters were examined using micro-computed tomography. The odontogenic potential of human pulp stem cells exposed to 30 mM glucose was assessed through alkaline phosphatase assays, examination of gene expression for dentin matrix protein 1 and dentin sialoprotein using real-time PCR, and alizarin red staining for calcium deposition.

Results: Along with reduced dentin thickness and root length in diabetic rats, the results revealed a significant increase in histone deacetylase 3 and 2 gene expressions in isolated diabetic pulp tissues compared to the control groups. The gene expression of odontogenic-related markers and alkaline phosphatase activity in human cultured pulp stem cells under hyperglycemic conditions significantly decreased. Adding Valproic acid and Trichostatin A restored the odontogenic differentiation markers, including calcium deposition, gene expression of dentin sialophosphoprotein, dentin matrix protein 1, and alkaline phosphatase activity.

Conclusion: The data suggests that hyperglycemic conditions negatively impact the odontogenic potential of pulp mesenchymal stem cells. However, histone deacetylase inhibitors improve the impaired odontogenic differentiation capacity. This study implies that histone deacetylases may represent a potential therapeutic target for enhancing the regenerative mineralization of pulp cells in diabetic patients.

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