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

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 st...

Full description

Bibliographic Details
Main Authors: Yuan Yuan, Honglue Tan, Pengyi Dai
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2017-08-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/479991
_version_ 1819277861357355008
author Yuan Yuan
Honglue Tan
Pengyi Dai
author_facet Yuan Yuan
Honglue Tan
Pengyi Dai
author_sort Yuan Yuan
collection DOAJ
description 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.
first_indexed 2024-12-24T00:02:50Z
format Article
id doaj.art-a4f86fda87bb4b26b65a6167ed3d8a08
institution Directory Open Access Journal
issn 1015-8987
1421-9778
language English
last_indexed 2024-12-24T00:02:50Z
publishDate 2017-08-01
publisher Cell Physiol Biochem Press GmbH & Co KG
record_format Article
series Cellular Physiology and Biochemistry
spelling doaj.art-a4f86fda87bb4b26b65a6167ed3d8a082022-12-21T17:25:05ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-08-014262159216810.1159/000479991479991Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13Yuan YuanHonglue TanPengyi DaiBackground/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.http://www.karger.com/Article/FullText/479991Krüppel-like factor 2 (KLF2)Matrix metalloproteinases (MMP)-13Type II collagenInterleukin-1βOsteoarthritis
spellingShingle Yuan Yuan
Honglue Tan
Pengyi Dai
Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
Cellular Physiology and Biochemistry
Krüppel-like factor 2 (KLF2)
Matrix metalloproteinases (MMP)-13
Type II collagen
Interleukin-1β
Osteoarthritis
title Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
title_full Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
title_fullStr Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
title_full_unstemmed Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
title_short Krüppel-Like Factor 2 Regulates Degradation of Type II Collagen by Suppressing the Expression of Matrix Metalloproteinase (MMP)-13
title_sort kruppel like factor 2 regulates degradation of type ii collagen by suppressing the expression of matrix metalloproteinase mmp 13
topic Krüppel-like factor 2 (KLF2)
Matrix metalloproteinases (MMP)-13
Type II collagen
Interleukin-1β
Osteoarthritis
url http://www.karger.com/Article/FullText/479991
work_keys_str_mv AT yuanyuan kruppellikefactor2regulatesdegradationoftypeiicollagenbysuppressingtheexpressionofmatrixmetalloproteinasemmp13
AT hongluetan kruppellikefactor2regulatesdegradationoftypeiicollagenbysuppressingtheexpressionofmatrixmetalloproteinasemmp13
AT pengyidai kruppellikefactor2regulatesdegradationoftypeiicollagenbysuppressingtheexpressionofmatrixmetalloproteinasemmp13