Cited by 107Protease and Inhibitor MechanismsBone and Dental Protein StudiesAlkaline Phosphatase Research Studies

Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis

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Shi, Joanne, Son, Mi-Young, Yamada, Susan, Szabova, Ludmila, Kahan, Stacie, Chrysovergis, Kaliopi, Wolf, Lauren, Surmak, Andrew +1 more·2008·Developmental Biology

Abstract

Peri-cellular remodeling of mesenchymal extracellular matrices is considered a prerequisite for cell proliferation, motility and development. Here we demonstrate that membrane-type 3 MMP, MT3-MMP, is expressed in mesenchymal tissues of the skeleton and in peri-skeletal soft connective tissue. Consistent with this localization, MT3-MMP-deficient mice display growth inhibition tied to a decreased viability of mesenchymal cells in skeletal tissues. We document that MT3-MMP works as a major collagenolytic enzyme, enabling cartilage and bone cells to cleave high-density fibrillar collagen and modulate their resident matrix to make it permissive for proliferation and migration. Collectively, these data uncover a novel extracellular matrix remodeling mechanism required for proper function of mesenchymal cells. The physiological significance of MT3-MMP is highlighted in mice double deficient for MT1-MMP and MT3-MMP. Double deficiency transcends the combined effects of the individual single deficiencies and leads to severe embryonic defects in palatogenesis and bone formation incompatible with life. These defects are directly tied to loss of indispensable collagenolytic activities required in collagen-rich mesenchymal tissues for extracellular matrix remodeling and cell proliferation during embryogenesis.

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Crossref · 10.1016/j.ydbio.2007.10.017

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49 of 49 references verified0 citation errors · 0 not checkable

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  • While osteoclasts express both cathepsin K and MMPs, which contribute differently to bone resorption, BLCs do not express cathepsin K but can efficiently remove nonmineralized fibrillary collagen mediated through their highly active MMPs.

    “While osteoclasts express both of these enzymes types, which contribute differently to bone resorption,120 BLCs do not express cathepsin K but can efficiently remove nonmineralized fibrillary collagen (present either on the quiescent bone surface or in resorption lacunae after osteoclastic activity)113 mediated through their highly active MMPs.121”

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Authors
Shi, J., Son, M.-Y., Yamada, S., Szabova, L., Kahan, S., Chrysovergis, K., Wolf, L., Surmak, A., & Holmbeck, K.
Affiliations
National Institutes of Health (US)
Corresponding author
Holmbeck, Kenn
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2008-01
Volume
313
Issue
1
Pages
196-209
ISSN
0012-1606 (ISSN-L)
OpenAlex
W2012083187
Cited by
107
References
49
Citations by year
2026: 4 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 4 · 2012: 7
FWCI
2.58
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 DE999999)
  • National Institute of Dental and Craniofacial Research (Z01DE000676)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords
MT3-MMP, MT1-MMP, extracellular matrix remodeling, collagen degradation, fibrillar collagen, mesenchymal cell proliferation, cell migration, embryonic development, palatogenesis, bone formation, cartilage
MeSH terms
Metallothionein 3, Animals, Collagen, Extracellular Matrix, Mesoderm, Osteogenesis, Palate, Skull, Mice, Knockout, Cell Proliferation, Mice, Matrix Metalloproteinase 14, Matrix Metalloproteinase 16

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