Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin B expression by rat normal chondrocytes.
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-1beta expression was also signifi cantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1beta. 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-1beta 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.
Doi
Hideyuki
H
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama 700-8558, Japan.
Nishida
Keiichiro
K
Yorimitsu
Masanori
M
Komiyama
Takamitsu
T
Kadota
Yasutaka
Y
Tetsunaga
Tomonori
T
Yoshida
Aki
A
Kubota
Satoshi
S
Takigawa
Masaharu
M
Ozaki
Toshifumi
T
D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D015847:Interleukin-4; D002401:Cathepsin B; D053509:Matrix Metalloproteinase 13