Beneficial effect of galectin 9 on rheumatoid arthritis by induction of apoptosis of synovial fibroblasts.
Arthritis Rheum
; 56(12): 3968-76, 2007 Dec.
Article
in En
| MEDLINE
| ID: mdl-18050192
ABSTRACT
OBJECTIVE:
To compare the expression of galectin 9 (Gal-9) in synovial tissue (ST) from rheumatoid arthritis (RA) patients and osteoarthritis (OA) patients and to evaluate the effects of Gal-9 on fibroblast-like synoviocytes (FLS) in these patients.METHODS:
The expression of Gal-9 in ST and FLS was compared using immunohistochemical techniques. Apoptotic cells in RA and OA ST samples were detected by TUNEL assay. Apoptosis of FLS was analyzed by the sub-G(1) method in vitro. The in vivo suppressive effects of Gal-9 on collagen-induced arthritis (CIA) in a mouse model were also elucidated.RESULTS:
The percentage of Gal-9-positive cells in ST samples and the amount of Gal-9 in synovial fluid samples were significantly higher in patients with RA than in patients with OA, suggesting the involvement of Gal-9 in the development of RA. Compared with the 2 wild-type Gal-9 forms, stable Gal-9, a mutant protein resistant to proteolysis, significantly induced apoptosis of FLS from RA patients. In contrast, other galectins, such as Gal-1, Gal-3, and Gal-8, did not induce apoptosis or suppress the proliferation of human RA FLS. Stable Gal-9 preferentially induced apoptosis and suppressed the proliferation of RA FLS in vitro. It also induced apoptosis of cells in RA ST implanted into SCID mice in vivo. In a mouse model of CIA, apoptotic cells were detected in the joints of stable Gal-9-treated mice, but not phosphate buffered saline-treated mice, and suppressed CIA characterized by pannus formation with inflammatory cell infiltration and bone/cartilage destruction.CONCLUSION:
Gal-9-induced apoptosis of hyperproliferative RA FLS may play a critical role in the suppression of RA.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoarthritis
/
Arthritis, Rheumatoid
/
Synovial Membrane
/
Apoptosis
/
Galectins
/
Fibroblasts
Limits:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Arthritis Rheum
Year:
2007
Document type:
Article
Affiliation country:
Japan