Matrix metalloproteinase 13–deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development
Open accessAbstract
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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MMP-13 is predominantly expressed in lower intermediate and deep layers of cartilage in early OA, while aggrecanases are expressed in superficial cartilage.
“In the early phases of OA, MMP-13 is predominantly expressed in the lower intermediate and deep layers of human and mouse cartilage, whereas aggrecanases are expressed in the superficial cartilage [25,26].”
From Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β- induced catabolic gene expression in cartilage (2015) · cites this paper as [26]
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- Authors
- Little, C. B., Barai, A., Burkhardt, D., Smith, S. M., Fosang, A. J., Werb, Z., Shah, M., & Thompson, E. W.
- Affiliations
- The University of Sydney (AU)
- Royal Children's Hospital (AU)
- University of California, San Francisco (US)
- The University of Melbourne (AU)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2009-11-30
- Volume
- 60
- Issue
- 12
- Pages
- 3723-3733
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- PMC
- PMC2832925
- OpenAlex
- W2060951121
- Cited by
- 642
- References
- 54
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 39 · 2023: 38 · 2022: 43 · 2021: 42 · 2020: 59 · 2019: 42 · 2018: 35 · 2017: 46 · 2016: 41 · 2015: 42 · 2014: 34 · 2013: 36 · 2012: 29
- FWCI
- 18.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Arthritis Australia
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council (384414)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR046238, R01AR046238)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- matrix metalloproteinase-13, collagenase-3, osteoarthritis, cartilage erosion, chondrocyte hypertrophy, osteophytes, type X collagen, MMP-13 inhibitors
- MeSH terms
- Animals, Arthritis, Experimental, Calcinosis, Cartilage, Articular, Femur, Hypertrophy, Joints, Male, Osteoarthritis, Tibia, Mice, Knockout, Chondrocytes, Mice, Matrix Metalloproteinase 13, Aggrecans, Osteophyte
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