論文 - 詳細
| RRC ID | 52374 |
|---|---|
| 著者 | Yuan Y, Tan H, Dai P. |
| タイトル | Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13. |
| ジャーナル | Cell Physiol Biochem |
| Abstract |
BACKGROUND/AIMS:Krüppel-like factor 2 (KLF2) plays an essential role in the inhibition of endothelial cell and macrophage activation during the inflammatory process. However, the roles of KLF2 in chondrocytes and the pathological progression of osteoarthritis (OA) remain unknown. The aim of this study was to investigate the function of KLF2 in the inhibition of cartilage matrix destruction in chondrocytes. METHODS:RT-PCR and western blot analysis was used to determine the expression of KLF2 in human chondrocytes. Luciferase assay, ELISA assay and MMP-13 enzymatic activity assays were used to investigate the effects of KLF2 in regulating MMP-13 expression. Western blot analysis was used to examine the effects of KLF2 in suppressing degradation of type Ⅱ collagen. RESULTS:KLF2 is expressed in primary chondrocytes and is downregulated in OA chondrocytes. Expression of KLF2 in primary chondrocytes was reduced in response to IL-1β. Overexpression of KLF2 robustly inhibited IL-1β-induced MMP-13 expression. Conversely, knockdown of KLF2 markedly exacerbated MMP-13 expression. Mechanistically, KLF2 could suppress the activation of MMP-13 promoter. However, knockdown of KLF2 could promote the activation of MMP-13 promoter. Importantly, overexpression of KLF2 ameliorated the degradation of type Ⅱ collagen while silencing of KLF2 exacerbated the degradation of type Ⅱ collagen induced by IL-1β. CONCLUSIONS:KLF2 may be a potential therapeutic target for OA treatment. |
| 巻・号 | 42(6) |
| ページ | 2159-2168 |
| 公開日 | 2017-8-15 |
| DOI | 10.1159/000479991 |
| PII | 000479991 |
| PMID | 28873368 |
| MeSH | Cells, Cultured Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Collagen Type II / metabolism* Enzyme-Linked Immunosorbent Assay Gene Expression / drug effects Genes, Reporter Human Umbilical Vein Endothelial Cells Humans Interleukin-1beta / pharmacology Kruppel-Like Transcription Factors / antagonists & inhibitors Kruppel-Like Transcription Factors / genetics Kruppel-Like Transcription Factors / metabolism* Matrix Metalloproteinase 13 / analysis Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism* Osteoarthritis / metabolism Osteoarthritis / pathology Promoter Regions, Genetic RNA Interference RNA, Messenger / metabolism RNA, Small Interfering / metabolism Real-Time Polymerase Chain Reaction |
| IF | 5.5 |
| 引用数 | 12 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |