Therapeutic potential of Liuwei Dihuang pill against KDM7A and Wnt/β-catenin signaling pathway in diabetic nephropathy-related osteoporosis

被引：61

作者：

Liu, Ming Ming ^{[1
,2
]}

Dong, Rui ^{[3
]}

Hua, Zhen ^{[2
]}

Lv, Nan Ning ^{[1
]}

Ma, Yong ^{[2
]}

Huang, Gui Cheng ^{[2
]}

Cheng, Jian ^{[4
,5
]}

Xu, Hai Yan ^{[6
]}

机构：

[1] Lianyungang Second Peoples Hosp, Dept Orthoped Surg, Lianyungang, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Inst Traumatol & Orthoped, Nanjing, Jiangsu, Peoples R China

[3] Zhejiang Chinese Med Univ, Dept Orthopaed Surg, Affiliated Hosp 1, Hangzhou, Zhejiang, Peoples R China

[4] Xuzhou Cent Hosp, Dept Orthoped, Xuzhou, Jiangsu, Peoples R China

[5] Xuzhou Med Univ, Xuzhou Clin Sch, Xuzhou, Jiangsu, Peoples R China

[6] Xuzhou Med Univ, Dept Human Anat, Xuzhou, Jiangsu, Peoples R China

来源：

BIOSCIENCE REPORTS | 2020年 / 40卷

基金：

中国国家自然科学基金;

关键词：

DIFFERENTIATION; PROMOTES;

D O I：

10.1042/BSR20201778

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The effects of Liuwei Dihuang pill (LWDH) on diabetic nephropathy-related osteoporosis (DNOP) are unclear. The present study aimed to evaluate the effects of LWDHon KDM7A and Wnt/beta-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/beta-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-alpha, IL-6, IL-8, IL-1 beta, ALP, and TRAP, and increased the calcium, phosphorus in serum, as well as decreased the level of the calcium and 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 alpha-SMA, vimentin, KDM7A, Wnt1 and beta-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/beta-catenin pathway.

引用

页数：15

共 38 条

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