Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice.

Abstract

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.

CONCLUSION:

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.

• Authors: Lin Xu, Jacqueline Servais, Ilona Polur, Doil Kim, Peter L Lee, Kimberly Chung, Yefu Li
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 62 Issue 9 Pg. 2736-44 (Sep 2010) ISSN: 1529-0131 [Electronic] United States
• PMID: 20518074 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Collagen Type XI
• Receptors, Mitogen
• Discoidin Domain Receptors
• Receptor Protein-Tyrosine Kinases

Topics

• Animals
• Cartilage, Articular (metabolism, pathology)
• Collagen Type XI (deficiency, genetics)
• Discoidin Domain Receptors
• Disease Models, Animal
• Disease Progression
• Fluorescent Antibody Technique, Indirect
• Immunoenzyme Techniques
• Menisci, Tibial (surgery)
• Mice
• Mice, Knockout
• Osteoarthritis (genetics, metabolism, pathology)
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Receptors, Mitogen (genetics, metabolism)
• Stifle (metabolism, pathology, surgery)