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MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy

Melanoma inhibitory activity/cartilage-derived retinoicacid-sensitive protein (MIA/CD-RAP) is a protein expressed and secreted by chondrocytes and cartilaginous tissues. MIA/CD-RAP-deficient mice develop milder osteoarthritis than wildtype mice. In this study, we investigated MIA/CD-RAP downstream t...

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Autores principales: Staebler, Sebastian, Lichtblau, Adrian, Gurbiel, Slavyana, Schubert, Thomas, Riechers, Alexander, Rottensteiner-Brandl, Ulrike, Bosserhoff, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856983/
https://www.ncbi.nlm.nih.gov/pubmed/36672165
http://dx.doi.org/10.3390/cells12020229
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author Staebler, Sebastian
Lichtblau, Adrian
Gurbiel, Slavyana
Schubert, Thomas
Riechers, Alexander
Rottensteiner-Brandl, Ulrike
Bosserhoff, Anja
author_facet Staebler, Sebastian
Lichtblau, Adrian
Gurbiel, Slavyana
Schubert, Thomas
Riechers, Alexander
Rottensteiner-Brandl, Ulrike
Bosserhoff, Anja
author_sort Staebler, Sebastian
collection PubMed
description Melanoma inhibitory activity/cartilage-derived retinoicacid-sensitive protein (MIA/CD-RAP) is a protein expressed and secreted by chondrocytes and cartilaginous tissues. MIA/CD-RAP-deficient mice develop milder osteoarthritis than wildtype mice. In this study, we investigated MIA/CD-RAP downstream targets to explain this reduced disease development. As a possible mediator, we could detect matrix metalloproteinase 13 (MMP13), and the influence of MIA/CD-RAP on MMP13 regulation was analyzed in vitro using SW1353 chondrosarcoma cells and primary chondrocytes. The femoral head cartilage of WT and MIA/CD-RAP −/− mice were cultured ex vivo to further investigate MMP13 activity. Finally, osteoarthritis was surgically induced via DMM in C57BL/6 mice, and the animals were treated with an MIA/CD-RAP inhibitory peptide by subcutaneously implanted pellets. MMP13 was regulated by MIA/CD-RAP in SW1353 cells, and MIA/CD-RAP −/− murine chondrocytes showed less expression of MMP13. Further, IL-1β-treated MIA/CD-RAP −/− chondrocytes displayed less MMP13 expression and activity. Additionally, MIA/CD-RAP-deficient ex vivo cultured cartilage explants showed less MMP13 activity as well as reduced cartilage degradation. The mice treated with the MIA/CD-RAP inhibitory peptide showed less osteoarthritis development. Our findings revealed MIA/CD-RAP as a new regulator of MMP13 and highlighted its role as a potential new target for osteoarthritis therapy.
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spelling pubmed-98569832023-01-21 MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy Staebler, Sebastian Lichtblau, Adrian Gurbiel, Slavyana Schubert, Thomas Riechers, Alexander Rottensteiner-Brandl, Ulrike Bosserhoff, Anja Cells Article Melanoma inhibitory activity/cartilage-derived retinoicacid-sensitive protein (MIA/CD-RAP) is a protein expressed and secreted by chondrocytes and cartilaginous tissues. MIA/CD-RAP-deficient mice develop milder osteoarthritis than wildtype mice. In this study, we investigated MIA/CD-RAP downstream targets to explain this reduced disease development. As a possible mediator, we could detect matrix metalloproteinase 13 (MMP13), and the influence of MIA/CD-RAP on MMP13 regulation was analyzed in vitro using SW1353 chondrosarcoma cells and primary chondrocytes. The femoral head cartilage of WT and MIA/CD-RAP −/− mice were cultured ex vivo to further investigate MMP13 activity. Finally, osteoarthritis was surgically induced via DMM in C57BL/6 mice, and the animals were treated with an MIA/CD-RAP inhibitory peptide by subcutaneously implanted pellets. MMP13 was regulated by MIA/CD-RAP in SW1353 cells, and MIA/CD-RAP −/− murine chondrocytes showed less expression of MMP13. Further, IL-1β-treated MIA/CD-RAP −/− chondrocytes displayed less MMP13 expression and activity. Additionally, MIA/CD-RAP-deficient ex vivo cultured cartilage explants showed less MMP13 activity as well as reduced cartilage degradation. The mice treated with the MIA/CD-RAP inhibitory peptide showed less osteoarthritis development. Our findings revealed MIA/CD-RAP as a new regulator of MMP13 and highlighted its role as a potential new target for osteoarthritis therapy. MDPI 2023-01-05 /pmc/articles/PMC9856983/ /pubmed/36672165 http://dx.doi.org/10.3390/cells12020229 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Staebler, Sebastian
Lichtblau, Adrian
Gurbiel, Slavyana
Schubert, Thomas
Riechers, Alexander
Rottensteiner-Brandl, Ulrike
Bosserhoff, Anja
MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title_full MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title_fullStr MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title_full_unstemmed MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title_short MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy
title_sort mia/cd-rap regulates mmp13 and is a potential new disease-modifying target for osteoarthritis therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856983/
https://www.ncbi.nlm.nih.gov/pubmed/36672165
http://dx.doi.org/10.3390/cells12020229
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