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KMID : 0388220120190020073
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Journal of the Korean Rheumatism Association
2012 Volume.19 No. 2 p.73 ~ p.81
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Therapeutic Effect of a Recombinant βig-h3 Fragment-RGD Peptide for Chronic Inflammatory Arthritis
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Jang Ji-Ae
Kang Jin-Hee
Sa Keum-Hee
Han Seung-Woo
Seo Jae-Seok
Kim Kyung-Hoon
Nam Eon-Jeong
Kim In-San
Kang Young-Mo
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Abstract
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Objective: ?ig-h3 is a 68kDa extracellular matrix protein which is overexpressed in synovial tissues of rheumatoid arthritis (RA). Previous results proved that ?ig-h3 fragments are relevant to adhesion and migration of synovial fibroblast and angiogenesis through interaction with ?v?3 integrin. We designed a recombinant ?ig-h3 protein consisting of a fas-1 domain and RGD motif and evaluated the therapeutic efficacy in RA.
Methods: Inhibitory effect of adhesion and migration of NIH3T3 cell line was evaluated in 96 well microtiter and transwell plates coated with ?ig-h3. Clinical arthritis index was evaluated after treating CIA mice with MFK12. Immunohistochemical staining in synovial tissues were performed. Expression of transcripts and proteins of inflammatory mediators were analyzed by semi-quantitative RT-PCR and immunoblotting.
Results: Recombinant protein consisted of 4th fas-1 domain truncated for H1 and H2 sequences and RGD peptide (MFK12), had M.W. of 10.4kDa. ?ig-h3 mediated adhesion and migration of NIH3T3 cell line were significantly inhibited in a dose-dependent manner. Arthritis severity and incidence were efficiently reduced when CIA mice were treated with MFK12 at 30 mg/kg/day compared with the control. Immunohistochemical staining of joint tissues in MFK12 treated mice exhibited reduced angiogenesis. In treated mice, expression of transcripts regarding inflammatory mediators was markedly suppressed and immunoblotting of ICAM-1 and RANKL from whole extract of hind paws also showed a significant reduction.
Conclusion: This study shows that MFK12 is effective in treating RA, although further study is warranted to improve the therapeutic efficacy.
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KEYWORD
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Rheumatoid arthritis, Inflammation, βig-h3, collagen-induced arthritis, Fas-1
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