title: Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation.
abstract: OBJECTIVE
  Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.
  
  
  METHODS
  Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1.
  
  
  RESULTS
  MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13.
  
  
  CONCLUSIONS
  miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1.Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J. Y. Chen. Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation. Bone Joint Res 2016;5:523-530. DOI: 10.1302/2046-3758.510.BJR-2016-0074.R2.
authors: Department of Orthopaedics, Chinese PLA General Hospital, No.28 Fuxing Road,Haidian District,Beijing 100853,China and, Jinan Military General Hospital, No.25, Shifan Road, Tianqiao District, Jinan 250031, Shandong, China.
authors: Y
authors: Y
authors: Yuan
authors: Department of Orthopaedics, Chinese PLA General Hospital, General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: G Q
authors: GQ
authors: Zhang
authors: Department of Orthopaedics, Chinese PLA General Hospital, General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: W
authors: W
authors: Chai
authors: Department of Orthopaedics, Chinese PLA General Hospital, General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: M
authors: M
authors: Ni
authors: Department of Orthopaedics, Chinese PLA General Hospital, General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China.
authors: C
authors: C
authors: Xu
authors: Department of Orthopaedics, Chinese PLA General Hospital, General Hospital, No.28 Fuxing Road, Haidian District, Beijing 100853, China chenjiying5693@126.com.
authors: J Y
authors: JY
authors: Chen
keywords: FOXC1; IL-1β; MicroRNA-138; cartilage degradation; osteoarthritis