JaLCDOI 10.18926/AMO/30956
FullText URL fulltext.pdf
Author Doi, Hideyuki| Nishida, Keiichiro| Yorimitsu, Masanori| Komiyama, Takamitsu| Kadota, Yasutaka| Tetsunaga, Tomonori| Yoshida, Aki| Kubota, Satoshi| Takigawa, Masaharu| Ozaki, Toshifumi|
Abstract <p>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.</p>
Keywords IL-4 MMP cathepsin B mechanical stress aggrecanase
Amo Type Original Article
Published Date 2008-04
Publication Title Acta Medica Okayama
Volume volume62
Issue issue2
Publisher Okayama University Medical School
Start Page 119
End Page 126
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 18464888
Web of Sience KeyUT 000255297600008
JaLCDOI 10.18926/AMO/30749
FullText URL fulltext.pdf
Author Komiyama, Takamitsu| Nishida, Keiichiro| Yorimitsu, Masanori| Doi, Hideyuki| Miyazawa, Shinichi| Kitamura, Ai| Yoshida, Aki| Nasu, Yoshihisa| Abe, Nobuhiro| Ozaki, Toshifumi|
Abstract Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p&#60;0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR.
Keywords spontaneous hypertensive rats insulin like growth factor-1 vascular endothelial growth factor ossification disturbance osteonecrosis
Amo Type Article
Published Date 2006-06
Publication Title Acta Medica Okayama
Volume volume60
Issue issue3
Publisher Okayama University Medical School
Start Page 141
End Page 148
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16838042
Web of Sience KeyUT 000238503600001