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Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts
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-...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745902/ https://www.ncbi.nlm.nih.gov/pubmed/23984338 http://dx.doi.org/10.1155/2013/302392 |
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author | Chellaiah, Meenakshi A. Ma, Tao |
author_facet | Chellaiah, Meenakshi A. Ma, Tao |
author_sort | Chellaiah, Meenakshi A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3745902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-37459022013-08-27 Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts Chellaiah, Meenakshi A. Ma, Tao Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2013 2013-07-28 /pmc/articles/PMC3745902/ /pubmed/23984338 http://dx.doi.org/10.1155/2013/302392 Text en Copyright © 2013 M. A. Chellaiah and T. Ma. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chellaiah, Meenakshi A. Ma, Tao Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title | Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title_full | Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title_fullStr | Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title_full_unstemmed | Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title_short | Membrane Localization of Membrane Type 1 Matrix Metalloproteinase by CD44 Regulates the Activation of Pro-Matrix Metalloproteinase 9 in Osteoclasts |
title_sort | membrane localization of membrane type 1 matrix metalloproteinase by cd44 regulates the activation of pro-matrix metalloproteinase 9 in osteoclasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745902/ https://www.ncbi.nlm.nih.gov/pubmed/23984338 http://dx.doi.org/10.1155/2013/302392 |
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