MiR-140-3p Ameliorates the Progression of Osteoarthritis via Targeting CXCR4

被引:28
作者
Ren, Tiantian [1 ,2 ]
Wei, Peng [1 ]
Song, Qinghua [1 ]
Ye, Zhaohui [1 ]
Wang, Yangjian [1 ]
Huang, Lixin [2 ]
机构
[1] Ningbo First Hosp, Dept Orthopaed, Ningbo 315000, Zhejiang, Peoples R China
[2] Soochow Univ, Dept Orthopaed, Affiliated Hosp 1, Suzhou 215000, Jiangsu, Peoples R China
关键词
microRNA-140-3p; interleukin-1; beta; chemokine (C-X-C motif) receptor 4; proliferation; apoptosis; osteoarthritis; EXPRESSION; APOPTOSIS; CHONDROCYTES; ARTHRITIS; CARTILAGE; INVASION;
D O I
10.1248/bpb.b19-00959
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Osteoarthritis is a common disease character with progressive destruction of cartilage. MicroRNA (miR)-140-3p was validated as a biomarker for osteoarthritis. However, the mechanism by which miRNA-40-3p regulates osteoarthritis remains unclear. Thus, this study aims to evaluate the potential function of miRNA-140-3p during the pathogenesis of osteoarthritis. MiRNA-140-3p expression in tissue and CHON-001 chondrocyte cells was determined with quantitative real time (qRT)-PCR. In vitro osteoarthritis model was established by treatment of the chondrocyte cells CHON-001 with interleukin (IL) -1 beta. Cell proliferation and apoptosis were measured with cell counting kit-8 (CCK8) and Annexin V/propidium iodide (PI) apoptosis assay, respectively. Protein expressions were evaluated using Western blot. The target gene of miR-140-3p was predicted using Targetscan and miRDB. MiR-140-3p was downregulated in knee tissue from patients with osteoarthritis. IL -1 beta inhibited the proliferation of CHON-001 cells via inducing apoptosis. In addition, IL -1 beta significantly inhibited the expressions of collagen II and aggrecan and increased the level of matrix metalloproteinase (MMP)13. However, the effects of IL -1 beta could be ameliorated by the addition of miR-140-3p mimics. Moreover, luciferase reporter assay demonstrated CXCR4 as a target gene of miR-140-3p. IL-1 beta-induced upregulation of CXCR4 could be blocked by miR-140-3p mimics. Our study indicated that miR-140-3p could suppress the progression of osteoarthritis by directly targeting CXCR4. Therefore, miR-140-3p might serve as a potential therapeutic target for the treatment of osteoarthritis.
引用
收藏
页码:810 / 816
页数:7
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