| Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes |
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Hyung Jin Kim, Eun Kyung Bae, Jinhee Kim, Ji Young Chai, Chan Hong Jeon, Hoon Suk Cha, Kwang Sung Ahn, Eun Mi Koh |
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Seoul National University College of Medicine |
| 류마티스 섬유모세포양 활막세포에서 저산소증 및 사이토카인에 의한 Aggrecanase-1과 Aggrecanase-2 발현 조절 |
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김형진, Eun Kyung Bae, Jinhee Kim, Ji Young Chai, Chan Hong Jeon, Hoon Suk Cha, Kwang Sung Ahn, Eun Mi Koh |
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| Abstract |
Background : While aggrecanases (aggrecanase-1 and aggrecanase-2) are substantially responsible for cartilage aggrecan breakdown in rheumatoid arthritis (RA), not much information is available on the regulation or expression of the two key aggrecanases in rheumatoid fibroblast-like synoviocytes (FLS). The aim of this study is to determine the effect of hypoxia and several cytokines on the expression of the aggrecanases in rheumatoid FLS.
Methods
: FLS obtained from RA patients were cultured under hypoxic condition for 24 hours. Quantitative polymerase chain reaction assays for mRNA expression of aggrecanase-1 and aggrecanase-2 were performed on FLS cultured under hypoxia. Additionally, to see the effect of various cytokines, same experiments were conducted after treating FLS with IL-1β, IL-6, EGF, TGF-β and TNF-α, compared with control.
Results
: Hypoxia significantly increased both aggrecanase-1 and -2 mRNA expression in rheumatoid FLS compared with normoxia. IL-1β, IL-6, EGF, TGF-β and TNF-α upregulated the mRNA expression of aggrecanase-1. Both EGF and TGF-β upregulated the mRNA expression of aggrecanase-2, but TNF-α significantly downregulated the mRNA expression of aggrecanase-2.
Conclusions
: These results showed upregulation of aggrecanase-1 and -2 by hypoxia and differential regulation of aggrecanase-1 and -2 by various cytokines in rheumatoid FLS. It suggests that hypoxia and cytokines enhance the aggrecanase activity of RA FLS and contribute to joint destruction.
Key Words : Hypoxia, Aggrecanase, Rheumatoid arthritis |
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