BACKGROUND:Uric acid, as an endogenous antioxidant, exhibits anti-oxidative and anti-DNA damage effects, promotes osteogenic differentiation, and therefore has been paid more attentions. OBJECTIVE:To investigate the effects of different concentrations of uric acid on the expression of genes related to Wnt/β-catenin signaling pathways during osteogenic differentiation of human bone marrow mesenchymal stem cel s. METHODS:Healthy adult human bone marrow mesenchymal stem cel s were in vitro isolated by adherent culture of whole bone marrow. Passage 3 bone marrow mesenchymal stem cel s were induced to differentiate into osteoblasts using different concentrations of uric acid (0, 140, 280, 560μmol/L). Alkaline phosphatase activity, cel proliferation capacity, and Wnt-3αandβ-catenin mRNA expression in the Wnt signaling pathways were detected. RESULTS AND CONCLUSION:Alkaline phosphatase staining was positive. After treatment with uric acid, alkaline phosphatase activity and cel proliferation capacity were increased, the expression of Wnt signaling pathway-related genes Wnt-3a andβ-catenin was up-regulated in a dose-dependent manner. There were significant differences in the abovementioned indices between experimental groups and between each experimental group and control group (P<0.05). These findings suggest that uric acid up-regulates Wnt-3a/β-catenin signaling pathway and thereby promotes the osteogenic differentiation and proliferation of human bone marrow mesenchymal stem cel s in a dose-dependent manner.%背景：尿酸作为一种内源性的抗氧化剂，其抗氧化、抗DNA 损害作用及发挥促成骨作用近年受到关注。 目的：探讨不同浓度尿酸对人骨髓间充质干细胞向成骨细胞分化过程中 Wnt/β-catenin 信号通路相关基因表达的影响。 方法：采用全骨髓贴壁法体外分离培养健康成年人骨髓间充质干细胞，培养至第3代时，用含不同浓度尿酸(0，140，280，560μmol/L)的成骨诱导液进行成骨向诱导分化培养，检测细胞成骨分化过程中碱性磷酸酶活性、增殖能力以及Wnt信号通路中Wnt-3α，β-catenin mRNA的表达。 结果与结论：各组细胞碱性磷酸酶染色为阳性，尿酸干预后各组细胞碱性磷酸酶活性和增殖能力增高，Wnt信号通路相关基因 Wnt-3a、β-catenin 的表达上调，且呈现浓度依赖性，各指标在实验组与对照组间比较以及实验组组间比较，差异均有显著性意义(P<0.05)。结果显示尿酸可通过促进Wnt-3a/β-catenin信号通路进而促进骨髓间充质干细胞向成骨细胞增殖和分化，具有浓度依赖性。
展开▼
