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

Little, C.B., Barai, A., Burkhardt, D., Smith, S.M., Fosang, A.J., Werb, Z., Shah, M., & Thompson, E.W. (2009) Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis and Rheumatism, 60(12), pp. 3723-3733.

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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.

Impact and interest:

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ID Code: 72143
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):101
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 19950295
Additional URLs:
DOI: 10.1002/art.25002
ISSN: 1529-0131
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright © 2009 by the American College of Rheumatology
Deposited On: 27 May 2014 01:43
Last Modified: 29 May 2014 05:49

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