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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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Autores principales: Chellaiah, Meenakshi A., Ma, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
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.
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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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