Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin b expression by rat normal chondrocytes

Hideyuki Doi, Keiichiro Nishida, Masanori Yorimitsu, Takamitsu Komiyama, Yasutaka Kadota, Tomonori Tetsunaga, Aki Yoshida, Satoshi Kubota, Masaharu Takigawa, Toshihumi Ozaki

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1β expression was also significantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1β. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1β expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes. Copyright

Original languageEnglish
Article number7
Pages (from-to)119-126
Number of pages8
JournalActa Medica Okayama
Volume62
Issue number2
Publication statusPublished - Apr 2008

Fingerprint

Matrix Metalloproteinase 13
Cathepsins
Chondrocytes
Tensile stress
Interleukin-4
Cathepsin B
Mechanical Stress
Rats
Down-Regulation
Interleukin-1
Osteoarthritis
Gene Expression
Aggrecans
Gene expression
Collagen Type II
Interleukin-10
Cartilage
Up-Regulation
Cytokines
Messenger RNA

Keywords

  • Aggrecanase
  • cathepsin B
  • IL-4
  • Mechanical stress
  • MMP

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin b expression by rat normal chondrocytes. / Doi, Hideyuki; Nishida, Keiichiro; Yorimitsu, Masanori; Komiyama, Takamitsu; Kadota, Yasutaka; Tetsunaga, Tomonori; Yoshida, Aki; Kubota, Satoshi; Takigawa, Masaharu; Ozaki, Toshihumi.

In: Acta Medica Okayama, Vol. 62, No. 2, 7, 04.2008, p. 119-126.

Research output: Contribution to journalArticle

@article{d6a499402f1648c2a339fe40ef40f0e3,
title = "Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin b expression by rat normal chondrocytes",
abstract = "Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7{\%} elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1β expression was also significantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1β. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1β expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes. Copyright",
keywords = "Aggrecanase, cathepsin B, IL-4, Mechanical stress, MMP",
author = "Hideyuki Doi and Keiichiro Nishida and Masanori Yorimitsu and Takamitsu Komiyama and Yasutaka Kadota and Tomonori Tetsunaga and Aki Yoshida and Satoshi Kubota and Masaharu Takigawa and Toshihumi Ozaki",
year = "2008",
month = "4",
language = "English",
volume = "62",
pages = "119--126",
journal = "Acta Medica Okayama",
issn = "0386-300X",
publisher = "Okayama University",
number = "2",

}

TY - JOUR

T1 - Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin b expression by rat normal chondrocytes

AU - Doi, Hideyuki

AU - Nishida, Keiichiro

AU - Yorimitsu, Masanori

AU - Komiyama, Takamitsu

AU - Kadota, Yasutaka

AU - Tetsunaga, Tomonori

AU - Yoshida, Aki

AU - Kubota, Satoshi

AU - Takigawa, Masaharu

AU - Ozaki, Toshihumi

PY - 2008/4

Y1 - 2008/4

N2 - Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1β expression was also significantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1β. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1β expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes. Copyright

AB - Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1β expression was also significantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1β. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1β expression. Our results suggest that IL-4 might have a therapeutic value in the treatment of OA by downregulation of mechanical stress-induced MMP-13 and cathepsin B expression by chondrocytes. Copyright

KW - Aggrecanase

KW - cathepsin B

KW - IL-4

KW - Mechanical stress

KW - MMP

UR - http://www.scopus.com/inward/record.url?scp=45149131422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45149131422&partnerID=8YFLogxK

M3 - Article

VL - 62

SP - 119

EP - 126

JO - Acta Medica Okayama

JF - Acta Medica Okayama

SN - 0386-300X

IS - 2

M1 - 7

ER -