start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=1
article-no=
start-page=165
end-page=174
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201301
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway in cultured human chondrocytes
en-subtitle=
kn-subtitle=
en-abstract=
kn-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.
en-copyright=
kn-copyright=

en-aut-name=SaitoT.
en-aut-sei=Saito
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NishidaK.
en-aut-sei=Nishida
en-aut-mei=K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FurumatsuT.
en-aut-sei=Furumatsu
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoshidaA.
en-aut-sei=Yoshida
en-aut-mei=A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OzawaM.
en-aut-sei=Ozawa
en-aut-mei=M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OzakiT.
en-aut-sei=Ozaki
en-aut-mei=T.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Human Morphol

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Orthopaed Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dens & Pharmaceut Sci, Dept Orthopaed Surg
en-keyword=Chondrocyte
kn-keyword=Chondrocyte
en-keyword=Mechanical stress
kn-keyword=Mechanical stress
en-keyword=RUNX-2
kn-keyword=RUNX-2
en-keyword=Aggrecanase
kn-keyword=Aggrecanase
en-keyword=ADAMTS
kn-keyword=ADAMTS
en-keyword=Histone deacetylase inhibitor
kn-keyword=Histone deacetylase inhibitor
END