Increased expression of discoidin domain receptor 2 is linked to the degree of cartilage damage in human knee joints: a potential role in osteoarthritis pathogenesis.
OBJECTIVE
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.


CONCLUSIONS
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.
Sunk
Ilse-Gerlinde
IG
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Bobacz
Klaus
K
Hofstaetter
Jochen G
JG
Amoyo
Love
L
Soleiman
Afschin
A
Smolen
Josef
J
Xu
Lin
L
Li
Yefu
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D024043:Collagen Type II / Q000494:pharmacology; D000070818:Discoidin Domain Receptors; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000235:genetics* / Q000378:metabolism*; D012720:Severity of Illness Index
D024043:Collagen Type II; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D053509:Matrix Metalloproteinase 13