Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development.

Abstract

OBJECTIVE:
To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA).

METHODS:
OA was surgically induced in the knees of MMP-13-knockout mice and wild-type mice, and mice were compared.

Histologic scoring of femoral and tibial cartilage aggrecan loss (0-3 scale), erosion (0-7 scale), and chondrocyte hypertrophy (0-1 scale), as well as osteophyte size (0-3 scale) and maturity (0-3 scale) was performed.

Serial sections were stained for type X collagen and the MMP-generated aggrecan neoepitope DIPEN.

RESULTS:
Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (P<0.01) and tibial cartilage erosion increased with time (P<0.05) in wild-type mice.

Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (P<0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks.

There was less tibial cartilage erosion in knockout mice than in wild-type mice at 8 weeks (P<0.02). Cartilaginous osteophytes were larger in knockout mice at 4 weeks (P<0.01), but by 8 weeks osteophyte maturity and size were no different from those in wild-type mice.

Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both wild-type and knockout mouse joints.

CONCLUSION:
Our findings indicate that structural cartilage damage in a mouse model of OA is dependent on MMP-13 activity.

Chondrocyte hypertrophy is not regulated by MMP-13 activity in this model and does not in itself lead to cartilage erosion. MMP-13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP-13 inhibitors.

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Subjects

Authors

Publication date

2009-12-16

Journal

Arthritis and rheumatism
Arthritis Rheum (0004-3591)

Journal topics

Language

Eng.

Copyright

Arthritis and rheumatism

Raymond Purves Research Laboratories, University of Sydney at Royal North Shore Hospital, St. Leonard's, New South Wales, Australia. cblittle [at] med.usyd.edu.au

Release reference

Arthritis Rheum. 2009 Dec;60(12):3723-33