MT1-MMP-Deficient Mice Develop Dwarfism, Osteopenia, Arthritis, and Connective Tissue Disease due to Inadequate Collagen Turnover
Open accessAbstract
MT1-MMP is a membrane-bound matrix metalloproteinase (MT-MMP) capable of mediating pericellular proteolysis of extracellular matrix components. MT1-MMP is therefore thought to be an important molecular tool for cellular remodeling of the surrounding matrix. To establish the biological role of this membrane proteinase we generated MT1-MMP-deficient mice by gene targeting. MT1-MMP deficiency causes craniofacial dysmorphism, arthritis, osteopenia, dwarfism, and fibrosis of soft tissues due to ablation of a collagenolytic activity that is essential for modeling of skeletal and extraskeletal connective tissues. Our findings demonstrate the pivotal function of MT1-MMP in connective tissue metabolism, and illustrate that modeling of the soft connective tissue matrix by resident cells is essential for the development and maintenance of the hard tissues of the skeleton.
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MT1-MMP-knockout mice usually die a couple of months after birth and display a severe phenotype including delayed ossification, unclosed sutures and unremoved cartilage.
“MT1-MMP-knockout (KO) mice usually die couple of months after birth, and display a severe phenotype that includes delayed ossification, unclosed sutures and unremoved cartilage.148”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [148]
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- Authors
- Holmbeck, K., Bianco, P., Caterina, J., Yamada, S., Kromer, M., Kuznetsov, S. A., Mankani, M., Gehron Robey, P., Poole, A. R., Pidoux, I., Ward, J. M., & Birkedal-Hansen, H.
- Affiliations
- National Institute of Dental and Craniofacial Research (US)
- University of L'Aquila (IT)
- Shriners Hospitals for Children - Canada (CA)
- National Cancer Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 99
- Issue
- 1
- Pages
- 81-92
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2016484384
- Cited by
- 1,298
- References
- 53
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 16 · 2023: 22 · 2022: 32 · 2021: 34 · 2020: 35 · 2019: 40 · 2018: 36 · 2017: 44 · 2016: 40 · 2015: 48 · 2014: 45 · 2013: 45 · 2012: 47
- FWCI
- 21.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- MT1-MMP, matrix metalloproteinases, collagen turnover, collagen degradation, connective tissue remodeling, osteopenia, dwarfism, arthritis, craniofacial dysmorphism, soft tissue fibrosis, extracellular matrix proteolysis, skeletal development
- MeSH terms
- Animals, Arthritis, Body Constitution, Bone Development, Bone Diseases, Metabolic, Bone Resorption, Cachexia, Cartilage, Collagen, Connective Tissue Diseases, Disease Models, Animal, Dwarfism, Fibrosis, Growth Plate, Hyalin, Metalloendopeptidases, Osteoblasts, Skin, Skull, Synovial Membrane, Stromal Cells, Mice, Knockout, Matrix Metalloproteinases, Mice, Matrix Metalloproteinases, Membrane-Associated, Matrix Metalloproteinase 14
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