Regulation of aggrecanase-1 and aggrecanase-2 expressions by hypoxia and cytokines in rheumatoid fibroblast-like synoviocytes.
- Author:
Hyung Jin KIM
1
;
Eun Kyung BAE
;
Jinhee KIM
;
Ji Young CHAI
;
Chan Hong JEON
;
Hoon Suk CHA
;
Kwang Sung AHN
;
Eun Mi KOH
Author Information
1. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea. chjeon@gmail.com
- Publication Type:Original Article
- Keywords:
Hypoxia;
Aggrecanase;
Rheumatoid arthritis
- MeSH:
Aggrecans;
Anoxia*;
Arthritis, Rheumatoid;
Cartilage;
Cytokines*;
Epidermal Growth Factor;
Humans;
Interleukin-6;
Joints;
Polymerase Chain Reaction;
RNA, Messenger;
Transforming Growth Factor beta;
Tumor Necrosis Factor-alpha;
Up-Regulation
- From:Korean Journal of Medicine
2006;71(2):182-188
- CountryRepublic of Korea
- Language:Korean
-
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-1beta, IL-6, EGF, TGF-beta and TNF-alpha, compared with control. RESULTS: Hypoxia significantly increased both aggrecanase-1 and -2 mRNA expression in rheumatoid FLS compared with normoxia. IL-1beta, IL-6, EGF, TGF-beta and TNF-alpha upregulated the mRNA expression of aggrecanase-1. Both EGF and TGF-beta upregulated the mRNA expression of aggrecanase-2, but TNF-alpha 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.
