Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice.
OBJECTIVE
To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA).


METHODS
Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry.


RESULTS
The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by ∼6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2(+/-) mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13.


CONCLUSIONS
Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.
Xu
Lin
L
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Servais
Jacqueline
J
Polur
Ilona
I
Kim
Doil
D
Lee
Peter L
PL
Chung
Kimberly
K
Li
Yefu
Y
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D024161:Collagen Type XI / Q000172:deficiency / Q000235:genetics; D000070818:Discoidin Domain Receptors; D004195:Disease Models, Animal; D018450:Disease Progression; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics* / Q000378:metabolism; D013264:Stifle / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D024161:Collagen Type XI; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases