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ID 51042
FullText URL
Author
Saito, T.
Nishida, K.
Furumatsu, T.
Yoshida, A.
Ozawa, M.
Ozaki, T.
Abstract
Objective: To investigate the inhibitory effects and the regulatory mechanisms of histone deacetylase (HDAC) inhibitors on mechanical stress-induced gene expression of runt-related transcription factor (RUNX)-2 and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 in human chondrocytes. Methods: Human chondrocytes were seeded in stretch chambers at a concentration of 5 x 10(4) cells/chamber. Cells were pre-incubated with or without HDAC inhibitors (MS-275 or trichostatin A; TSA) for 12 h, followed by uniaxial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation), which was applied for 30 min using the ST-140-10 system (STREX, Osaka, Japan). Total RNA was extracted and the expression of RUNX-2, ADAMTS-5, matrix metalloproteinase (MMP)-3, and MMP-13 at the mRNA and protein levels were examined by real-time polymerase chain reaction (PCR) and immunocytochemistry, respectively. The activation of diverse mitogen-activated protein kinase (MAPK) pathways with or without HDAC inhibitors during CTS was examined by western blotting. Results: HDAC inhibitors (TSA: 10 nM, MS-275: 100 nM) suppressed CTS-induced expression of RUNX-2, ADAMTS-5, and MMP-3 at both the mRNA and protein levels within 1 h. CTS-induced activation of p38 MAPK (p38), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (INK) MAPKs was downregulated by both HDAC inhibitors. Conclusion: The CTS-induced expression of RUNX-2 and ADAMTS-5 was suppressed by HDAC inhibitors via the inhibition of the MAPK pathway activation in human chondrocytes. The results of the current study suggested a novel therapeutic role for HDAC inhibitors against degenerative joint disease such as osteoarthritis.
Keywords
Chondrocyte
Mechanical stress
RUNX-2
Aggrecanase
ADAMTS
Histone deacetylase inhibitor
Published Date
2013-01
Publication Title
Osteoarthritis and Cartilage
Volume
volume21
Issue
issue1
Publisher
Elsevier Ltd
Start Page
165
End Page
174
ISSN
1063-4584
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.joca.2012.09.003
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/50692
language
英語
Copyright Holders
(C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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author
Refereed
True
DOI
Web of Sience KeyUT