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.
Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA.
Lin
L
Xu
Jacqueline
J
Servais
Ilona
I
Polur
Doil
D
Kim
Peter L
PL
Lee
Kimberly
K
Chung
Yefu
Y
Li
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