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Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy

BACKGROUND: Muscle atrophy impacts almost every patient seen for orthopaedic conditions. Unfortunately, no effective treatment is available to date. Matrix metalloproteinases (MMPs), especially MMP-2, are involved in skeletal muscle atrophy. MMP-2 null mice reportedly have substantially reduced musc...

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Detalles Bibliográficos
Autor principal: Liu, Xuhui
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094615/
https://www.ncbi.nlm.nih.gov/pubmed/21132408
http://dx.doi.org/10.1007/s11999-010-1726-5
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author Liu, Xuhui
author_facet Liu, Xuhui
author_sort Liu, Xuhui
collection PubMed
description BACKGROUND: Muscle atrophy impacts almost every patient seen for orthopaedic conditions. Unfortunately, no effective treatment is available to date. Matrix metalloproteinases (MMPs), especially MMP-2, are involved in skeletal muscle atrophy. MMP-2 null mice reportedly have substantially reduced muscle atrophy after tendon transection compared with wild-type mice, suggesting MMP-2 plays an important role in muscle atrophy. Although the exact mechanisms remain unknown, a newly-discovered intracellular form of MMP-2 suggests a possible novel mechanism of MMP-2 digesting muscle matrix during muscle atrophy. I propose a new pharmacologic treatment for muscle atrophy using selective MMP-2 inhibitors. QUESTIONS/HYPOTHESIS: I hypothesize: (1) intracellular MMP-2 plays an important role during muscle atrophy by digesting intramuscular matrix; (2) AP-1 and NFAT signal transduction pathways are responsible for expression and activation of the intracellular MMP-2 during muscle atrophy; and (3) specific MMP-2 inhibitors can serve as a novel pharmacologic strategy in treating disuse-induced muscle atrophy. METHOD OF STUDY: Expression and activity of extracellular and intracellular MMP-2 will be determined in a mouse tendon transection model. The role of AP-1 and NFAT signal transduction pathways in MMP-2 transcriptional regulation in muscle atrophy will be determined using chromatin-immunoprecipitation (ChIP) and small interfering RNA (siRNA). I also will test the feasibility of treating muscle atrophy using selective MMP-2 inhibitors. SIGNIFICANCE: Understanding the signaling transduction pathway of extracellular and intracellular MMP-2 expression during muscle atrophy may lead to novel treatments for muscle atrophy that preserve the normal physiologic function of MMP-2.
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spelling pubmed-30946152011-07-14 Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy Liu, Xuhui Clin Orthop Relat Res Emerging Ideas BACKGROUND: Muscle atrophy impacts almost every patient seen for orthopaedic conditions. Unfortunately, no effective treatment is available to date. Matrix metalloproteinases (MMPs), especially MMP-2, are involved in skeletal muscle atrophy. MMP-2 null mice reportedly have substantially reduced muscle atrophy after tendon transection compared with wild-type mice, suggesting MMP-2 plays an important role in muscle atrophy. Although the exact mechanisms remain unknown, a newly-discovered intracellular form of MMP-2 suggests a possible novel mechanism of MMP-2 digesting muscle matrix during muscle atrophy. I propose a new pharmacologic treatment for muscle atrophy using selective MMP-2 inhibitors. QUESTIONS/HYPOTHESIS: I hypothesize: (1) intracellular MMP-2 plays an important role during muscle atrophy by digesting intramuscular matrix; (2) AP-1 and NFAT signal transduction pathways are responsible for expression and activation of the intracellular MMP-2 during muscle atrophy; and (3) specific MMP-2 inhibitors can serve as a novel pharmacologic strategy in treating disuse-induced muscle atrophy. METHOD OF STUDY: Expression and activity of extracellular and intracellular MMP-2 will be determined in a mouse tendon transection model. The role of AP-1 and NFAT signal transduction pathways in MMP-2 transcriptional regulation in muscle atrophy will be determined using chromatin-immunoprecipitation (ChIP) and small interfering RNA (siRNA). I also will test the feasibility of treating muscle atrophy using selective MMP-2 inhibitors. SIGNIFICANCE: Understanding the signaling transduction pathway of extracellular and intracellular MMP-2 expression during muscle atrophy may lead to novel treatments for muscle atrophy that preserve the normal physiologic function of MMP-2. Springer-Verlag 2010-12-04 2011-06 /pmc/articles/PMC3094615/ /pubmed/21132408 http://dx.doi.org/10.1007/s11999-010-1726-5 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Emerging Ideas
Liu, Xuhui
Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title_full Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title_fullStr Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title_full_unstemmed Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title_short Emerging Ideas: Matrix Metalloproteinase-2 in Muscle Atrophy
title_sort emerging ideas: matrix metalloproteinase-2 in muscle atrophy
topic Emerging Ideas
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094615/
https://www.ncbi.nlm.nih.gov/pubmed/21132408
http://dx.doi.org/10.1007/s11999-010-1726-5
work_keys_str_mv AT liuxuhui emergingideasmatrixmetalloproteinase2inmuscleatrophy