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Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis.
Bioscience Reports ( IF 4 ) Pub Date : 2020-09-11 , DOI: 10.1042/bsr20201778 Ming Ming Liu 1, 2 , Rui Dong 3 , Zhen Hua 2 , Nan Ning Lv 1 , Yong Ma 2 , Gui Cheng Huang 2 , Jian Cheng 4, 5 , Hai Yan Xu 6
Bioscience Reports ( IF 4 ) Pub Date : 2020-09-11 , DOI: 10.1042/bsr20201778 Ming Ming Liu 1, 2 , Rui Dong 3 , Zhen Hua 2 , Nan Ning Lv 1 , Yong Ma 2 , Gui Cheng Huang 2 , Jian Cheng 4, 5 , Hai Yan Xu 6
Affiliation
The effects of Liuwei Dihuang Pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. This study aimed to evaluate the effects of LWDH on KDM7A and Wnt/β-catenin signaling pathway in DNOP rats and the high glucose-induced MC3T3-E1 cells. A DNOP model was prepared by streptozotocin in 9-week old male Sprague-Dawley(SD) rats to evaluate the effects of LWDH. The cell viability and differentiation capacity of high glucose-induced MC3T3-E1 cells were determined by CCK-8 assay, Alizarin Red staining, and alkaline phosphatase (ALP) staining, respectively. Furthermore, the expressions of KDM7A and Wnt1/β-catenin pathway-related proteins were determined by western blot analysis. Treatment of DNOP rats with LWDH could significantly ameliorate the general state, degradation of renal function, and renal pathological changes. LWDH decreased the levels of TNF-α, IL-6, IL-8, IL-1β, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium, phosphorus in the urine. Besides, LWDH significantly improved bone mineral density (BMD), bone volume (BV), and the bone microstructure of DNOP rats. Moreover, LWDH increased the levels of the elastic modulus, ultimate load, and bending strength in the femurs. In MC3T3-E1 cells, serum-containing LWDH significantly increases in cell viability and osteoblastic differentiation capability. The expression of α-SMA, vimentin, KDM7A, Wnt1, β-catenin, were significantly down-regulated, and the E-cadherin, H3K9-Me2, H3K27-Me2, BMP-4, BMP-7, Runx2, osteocalcin, and Col1a1 were significantly up-regulated with LWDH treatment. The present study shows that LWDH has a therapeutic effect on DNOP, in part, through down-regulation of KDM7A and Wnt/β-catenin pathway.
中文翻译:
六味地黄丸对糖尿病肾病相关性骨质疏松症的KDM7A和Wnt /β-catenin信号通路的治疗潜力。
六味地黄丸(LWDH)对糖尿病肾病相关性骨质疏松症(DNOP)的作用尚不清楚。这项研究旨在评估LWDH对DNOP大鼠和高糖诱导的MC3T3-E1细胞中KDM7A和Wnt /β-catenin信号通路的影响。用链脲佐菌素在9周大的雄性Sprague-Dawley(SD)大鼠中制备DNOP模型,以评估LWDH的作用。通过CCK-8分析,茜素红染色和碱性磷酸酶(ALP)染色分别测定高糖诱导的MC3T3-E1细胞的细胞活力和分化能力。此外,通过蛋白质印迹分析确定了KDM7A和Wnt1 /β-catenin途径相关蛋白的表达。用LWDH治疗DNOP大鼠可以显着改善其总体状态,肾功能退化和肾脏病理变化。LWDH降低了TNF-α,IL-6,IL-8,IL-1β,ALP和TRAP的水平,并增加了血清中的钙,磷,并降低了尿液中的钙,磷水平。此外,LWDH显着改善了DNOP大鼠的骨矿物质密度(BMD),骨体积(BV)和骨骼微结构。此外,LWDH增加了股骨的弹性模量,极限载荷和弯曲强度。在MC3T3-E1细胞中,含血清的LWDH的细胞活力和成骨细胞分化能力显着提高。α-SMA,波形蛋白,KDM7A,Wnt1,β-catenin的表达显着下调,E-钙黏着蛋白,H3K9-Me2,H3K27-Me2,BMP-4,BMP-7,Runx2,骨钙蛋白和Col1a1被LWDH处理显着上调。本研究表明LWDH对DNOP有治疗作用,
更新日期:2020-09-13
中文翻译:
六味地黄丸对糖尿病肾病相关性骨质疏松症的KDM7A和Wnt /β-catenin信号通路的治疗潜力。
六味地黄丸(LWDH)对糖尿病肾病相关性骨质疏松症(DNOP)的作用尚不清楚。这项研究旨在评估LWDH对DNOP大鼠和高糖诱导的MC3T3-E1细胞中KDM7A和Wnt /β-catenin信号通路的影响。用链脲佐菌素在9周大的雄性Sprague-Dawley(SD)大鼠中制备DNOP模型,以评估LWDH的作用。通过CCK-8分析,茜素红染色和碱性磷酸酶(ALP)染色分别测定高糖诱导的MC3T3-E1细胞的细胞活力和分化能力。此外,通过蛋白质印迹分析确定了KDM7A和Wnt1 /β-catenin途径相关蛋白的表达。用LWDH治疗DNOP大鼠可以显着改善其总体状态,肾功能退化和肾脏病理变化。LWDH降低了TNF-α,IL-6,IL-8,IL-1β,ALP和TRAP的水平,并增加了血清中的钙,磷,并降低了尿液中的钙,磷水平。此外,LWDH显着改善了DNOP大鼠的骨矿物质密度(BMD),骨体积(BV)和骨骼微结构。此外,LWDH增加了股骨的弹性模量,极限载荷和弯曲强度。在MC3T3-E1细胞中,含血清的LWDH的细胞活力和成骨细胞分化能力显着提高。α-SMA,波形蛋白,KDM7A,Wnt1,β-catenin的表达显着下调,E-钙黏着蛋白,H3K9-Me2,H3K27-Me2,BMP-4,BMP-7,Runx2,骨钙蛋白和Col1a1被LWDH处理显着上调。本研究表明LWDH对DNOP有治疗作用,