Polygalacic acid inhibits MMPs expression and osteoarthritis via Wnt/β-catenin and MAPK signal pathways suppression

被引:32
作者
Xu, Kai [1 ]
Ma, Chiyuan [1 ]
Xu, Langhai [1 ]
Ran, Jisheng [1 ]
Jiang, Lifeng [1 ]
He, Yuzhe [1 ]
Moqbel, Safwat Adel Abdo [1 ]
Wang, Zhan [1 ]
Wu, Lidong [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Orthoped Surg, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Polygalacic acid; Osteoarthritis; Matrix metalloproteinase; MAPK; Wnt/beta-catenin; TUMOR-NECROSIS-FACTOR; KNEE OSTEOARTHRITIS; GENE-EXPRESSION; CARTILAGE; CHONDROCYTES; RAT; MENISCUS; DEFECTS; MICE;
D O I
10.1016/j.intimp.2018.08.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Osteoarthritis (OA) is a chronic degenerative joint disease that has been shown to be closely related to the over expression of matrix metalloproteinases (MMPs). Polygalacic acid is a triterpene isolated from the root of Polygala tenuifolia Willd. In the present study, the anti-inflammatory effect of polygalacic acid in OA was investigated as well as its in vitro and in vivo mechanism. In vitro, rat chondrocytes were induced with interleukin-1beta (IL-1 beta) and treated with different concentrations of polygalacic acid; real-time PCR and Western blotting were performed to evaluate the expressions of MMP-3, MMP-9, MMP-13, and COX-2. In addition, the MAPK and Wnt/beta-catenin signaling pathways were analyzed via Western blotting and immunofluorescence staining. In vivo, a rat OA model was treated with polygalacic acid. Gross morphological and histological assessments were performed to evaluate the resulting cartilage damage. Polygalacic acid significantly reduced the expression of MMPs and COX-2, which could be induced by IL-1 beta in rat chondrocytes. Furthermore, polygalacic acid treatment prevented the degeneration of cartilage in the rat OA model. To investigate the underlying mechanism, we found that polygalacic acid suppressed both the IL-1 beta-induced activation of Wnt/beta-catenin and the mitogen-activated protein kinase (MAPK) signal pathway in chondrocytes. These results suggest that polygalacic acid may have a therapeutic effect in OA treatment.
引用
收藏
页码:246 / 252
页数:7
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