Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts
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CD44, MT1-MMP, and MMP9 are implicated in the migration of osteoclast and bone resorption. This study was designed to determine the functional relationship between CD44 and MT1-MMP in the activation of pro-MMP9. We used osteoclasts isolated from wild-type and CD44-null mice. Results showed that MT1-MMP is present in multiple forms with a molecular mass ~63, 55, and 45 kDa in the membrane of wild-type osteoclasts. CD44-null osteoclasts demonstrated a 55 kDa active MT1-MMP form in the membrane and conditioned medium. It failed to activate pro-MMP9 because TIMP2 binds and inhibits this MT1-MMP (~55 kDa) in CD44-null osteoclasts. The role of MT1-MMP in the activation of pro-MMP9, CD44 expression, and migration was confirmed by knockdown of MT1-MMP in wild-type osteoclasts. Although knockdown of MMP9 suppressed osteoclast migration, it had no effects on MT1-MMP activity or CD44 expression. These results suggest that CD44 and MT1-MMP are directly or indirectly involved in the regulation of pro-MMP9 activation. Surface expression of CD44, membrane localization of MT1-MMP, and activation of pro-MMP9 are the necessary sequence of events in osteoclast migration.
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MMP-9-knockout mice showed reduced osteoclast invasion into the core of developing bones, and in vitro osteoclasts lacking MMP9 did not migrate.
“MMP-9-KO mice showed reduced osteoclast invasion into the core of developing bones,151 and in vitro, osteoclasts lacking MMP9 did not migrate.152”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [152]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
- Authors
- Chellaiah, M. A., & Ma, T.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Chellaiah, Meenakshi A.
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2013
- Volume
- 2013
- Pages
- 1-13
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC3745902
- OpenAlex
- W2097648368
- Cited by
- 37
- References
- 59
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 4
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (AR46292)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- CD44, MT1-MMP, osteoclasts, osteoclast migration, bone resorption, TIMP-2, membrane localization
- MeSH terms
- Animals, Bone Resorption, Cell Membrane, Cell Movement, Enzyme Activation, Extracellular Matrix, Mice, Inbred C57BL, Molecular Weight, Osteoclasts, Protein Binding, Immunoblotting, Cell Polarity, Hyaluronan Receptors, Tissue Inhibitor of Metalloproteinase-2, Matrix Metalloproteinase 9, Protein Transport, RNA, Small Interfering, Mice, Matrix Metalloproteinase 14, Cell Migration Assays, Gene Knockdown Techniques
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