Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13

Autor: Pengyi Dai, Honglue Tan, Yuan Yuan
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
Interleukin-1beta
Matrix metalloproteinases (MMP)-13
Type II collagen
Kruppel-Like Transcription Factors
Gene Expression
Enzyme-Linked Immunosorbent Assay
Matrix metalloproteinase
Real-Time Polymerase Chain Reaction
lcsh:Physiology
Collagen receptor
lcsh:Biochemistry
03 medical and health sciences
0302 clinical medicine
Chondrocytes
Krüppel
Genes
Reporter
Matrix Metalloproteinase 13
Osteoarthritis
Human Umbilical Vein Endothelial Cells
Macrophage
Humans
lcsh:QD415-436
RNA
Messenger
RNA
Small Interfering
Promoter Regions
Genetic
Collagen Type II
Cells
Cultured
lcsh:QP1-981
Chemistry
Interleukin-1β
Cell biology
Endothelial stem cell
Interleukin 1β
030104 developmental biology
030220 oncology & carcinogenesis
KLF2
RNA Interference
Krüppel-like factor 2 (KLF2)
Zdroj: Cellular Physiology and Biochemistry, Vol 42, Iss 6, Pp 2159-2168 (2017)
ISSN: 1421-9778
1015-8987
Popis: 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.
Databáze: OpenAIRE
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