Therapeutic Effect of a Recombinant betaig-h3 Fragment-RGD Peptide for Chronic Inflammatory Arthritis
Journal of Rheumatic Diseases
;
: 73-81, 2012.
Article
in Korean
| WPRIM
| ID: wpr-15490
ABSTRACT
OBJECTIVE:
betaig-h3 is a 68kDa extracellular matrix protein which is overexpressed in synovial tissues of rheumatoid arthritis (RA). Previous results proved that betaig-h3 fragments are relevant to adhesion and migration of synovial fibroblast and angiogenesis through interaction with alphavbeta 3 integrin. We designed a recombinant betaig-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 betaig-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. betaig-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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oligopeptides
/
Arthritis
/
Arthritis, Experimental
/
Arthritis, Rheumatoid
/
Immunoblotting
/
Proteins
/
Cell Line
/
Incidence
/
Extracellular Matrix Proteins
/
Transforming Growth Factor beta
Type of study:
Incidence study
/
Prognostic study
Limits:
Animals
Language:
Korean
Journal:
Journal of Rheumatic Diseases
Year:
2012
Type:
Article
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