Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes
Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan ext...
Saved in:
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
2014
|
Online Access: | http://www.scopus.com/inward/record.url?eid=2-s2.0-80051614317&partnerID=40&md5=726ea14fa8963ec46471f65464198741 http://cmuir.cmu.ac.th/handle/6653943832/4639 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Chiang Mai University |
Language: | English |
id |
th-cmuir.6653943832-4639 |
---|---|
record_format |
dspace |
spelling |
th-cmuir.6653943832-46392014-08-30T02:42:41Z Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes Toegel S. Wu S.Q. Otero M. Goldring M.B. Leelapornpisid P. Chiari C. Kolb A. Unger F.M. Windhager R. Viernstein H. Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1β), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1β-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1β-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation. © 2011 Springer-Verlag. 2014-08-30T02:42:41Z 2014-08-30T02:42:41Z 2011 Article in Press 15558932 10.1007/s12263-011-0244-8 http://www.scopus.com/inward/record.url?eid=2-s2.0-80051614317&partnerID=40&md5=726ea14fa8963ec46471f65464198741 http://cmuir.cmu.ac.th/handle/6653943832/4639 English |
institution |
Chiang Mai University |
building |
Chiang Mai University Library |
country |
Thailand |
collection |
CMU Intellectual Repository |
language |
English |
description |
Exacerbated production of matrix metalloproteinases (MMPs) is a key event in the progression of osteoarthritis (OA) and represents a promising target for the management of OA with nutraceuticals. In this study, we sought to determine the MMP-inhibitory activity of an ethanolic Caesalpinia sappan extract (CSE) in human OA chondrocytes. Thus, human articular chondrocytes isolated from OA cartilage and SW1353 chondrocytes were stimulated with Interleukin-1beta (IL1β), without or with pretreatment with CSE. Following viability assays, the production of MMP-2 and MMP-13 was assessed using ELISA, whereas mRNA levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13 and TIMP-1, TIMP-2, TIMP-3 were quantified using RT-qPCR assays. Chondrocytes were co-transfected with a MMP-13 luciferase reporter construct and NF-kB p50 and p65 expression vectors in the presence or absence of CSE. In addition, the direct effect of CSE on the proteolytic activities of MMP-2 was evaluated using gelatin zymography. We found that CSE significantly suppressed IL1β-mediated upregulation of MMP-13 mRNA and protein levels via abrogation of the NF-kB(p65/p50)-driven MMP-13 promoter activation. We further observed that the levels of IL1β-induced MMP-1, MMP-3, MMP-7, and MMP-9 mRNA, but not TIMP mRNA levels, were down-regulated in chondrocytes in response to CSE. Zymographic results suggested that CSE did not directly interfere with the proteolytic activity of MMP-2. In summary, this study provides evidence for the MMP-inhibitory potential of CSE or CSE-derived compounds in human OA chondrocytes. The data indicate that the mechanism of this inhibition might, at least in part, involve targeting of NF-kB-mediated promoter activation. © 2011 Springer-Verlag. |
format |
Article |
author |
Toegel S. Wu S.Q. Otero M. Goldring M.B. Leelapornpisid P. Chiari C. Kolb A. Unger F.M. Windhager R. Viernstein H. |
spellingShingle |
Toegel S. Wu S.Q. Otero M. Goldring M.B. Leelapornpisid P. Chiari C. Kolb A. Unger F.M. Windhager R. Viernstein H. Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
author_facet |
Toegel S. Wu S.Q. Otero M. Goldring M.B. Leelapornpisid P. Chiari C. Kolb A. Unger F.M. Windhager R. Viernstein H. |
author_sort |
Toegel S. |
title |
Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
title_short |
Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
title_full |
Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
title_fullStr |
Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
title_full_unstemmed |
Caesalpinia sappan extract inhibits IL1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
title_sort |
caesalpinia sappan extract inhibits il1β-mediated overexpression of matrix metalloproteinases in human chondrocytes |
publishDate |
2014 |
url |
http://www.scopus.com/inward/record.url?eid=2-s2.0-80051614317&partnerID=40&md5=726ea14fa8963ec46471f65464198741 http://cmuir.cmu.ac.th/handle/6653943832/4639 |
_version_ |
1681420274999754752 |