In:
Arthritis & Rheumatism, Wiley, Vol. 56, No. 11 ( 2007-11), p. 3685-3692
Abstract:
To investigate the relationship between increased discoidin domain receptor 2 (DDR‐2) expression and cartilage damage in osteoarthritis (OA). Methods Full‐thickness cartilage tissue samples from 16 human knee joints were obtained and the grade of cartilage damage was evaluated according to the Mankin scale. Expression of DDR‐2, matrix metalloproteinase 13 (MMP‐13), and MMP‐derived type II collagen fragments was visualized immunohistochemically. Moreover, upon stimulation with either type II collagen or gelatin, levels of DDR‐2 and MMP‐13 messenger RNA (mRNA) in primary human articular chondrocytes were assessed by real‐time polymerase chain reaction. Results Immunohistochemical analysis showed an increase in DDR‐2 expression in human articular cartilage, which was correlated with the degree of tissue damage. In parallel, the extent of MMP‐13 and type II collagen breakdown products was elevated as a function of increased DDR‐2 expression and cartilage damage. Furthermore, in vitro experiments revealed an up‐regulation of both DDR‐2 and MMP‐13 mRNA in human articular chondrocytes after stimulation with type II collagen. Conclusion Our data indicate that 3 factors, DDR‐2 expression, MMP‐13 expression, and the degree of cartilage damage, are linked, such that DDR‐2 promotes tissue catabolism, and tissue degradation promotes DDR‐2 up‐regulation and activation. Thus, the perpetuation of DDR‐2 expression and activation can be seen as a vicious circle that ultimately leads to cartilage destruction in OA.
Type of Medium:
Online Resource
ISSN:
0004-3591
,
1529-0131
Language:
English
Publisher:
Wiley
Publication Date:
2007
detail.hit.zdb_id:
2014367-9
detail.hit.zdb_id:
2754614-7
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