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Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis

PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase β cleave...

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Autores principales: Das, Nabangshu, de Almeida, Luiz G. N., Derakhshani, Afshin, Young, Daniel, Mehdinejadiani, Kobra, Salo, Paul, Rezansoff, Alexander, Jay, Gregory D., Sommerhoff, Christian P., Schmidt, Tannin A., Krawetz, Roman, Dufour, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079686/
https://www.ncbi.nlm.nih.gov/pubmed/37024468
http://dx.doi.org/10.1038/s41467-023-37598-3
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author Das, Nabangshu
de Almeida, Luiz G. N.
Derakhshani, Afshin
Young, Daniel
Mehdinejadiani, Kobra
Salo, Paul
Rezansoff, Alexander
Jay, Gregory D.
Sommerhoff, Christian P.
Schmidt, Tannin A.
Krawetz, Roman
Dufour, Antoine
author_facet Das, Nabangshu
de Almeida, Luiz G. N.
Derakhshani, Afshin
Young, Daniel
Mehdinejadiani, Kobra
Salo, Paul
Rezansoff, Alexander
Jay, Gregory D.
Sommerhoff, Christian P.
Schmidt, Tannin A.
Krawetz, Roman
Dufour, Antoine
author_sort Das, Nabangshu
collection PubMed
description PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase β cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, −4, and −5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase β and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase β and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase β as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4.
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spelling pubmed-100796862023-04-08 Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis Das, Nabangshu de Almeida, Luiz G. N. Derakhshani, Afshin Young, Daniel Mehdinejadiani, Kobra Salo, Paul Rezansoff, Alexander Jay, Gregory D. Sommerhoff, Christian P. Schmidt, Tannin A. Krawetz, Roman Dufour, Antoine Nat Commun Article PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase β cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, −4, and −5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase β and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase β and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase β as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4. Nature Publishing Group UK 2023-04-06 /pmc/articles/PMC10079686/ /pubmed/37024468 http://dx.doi.org/10.1038/s41467-023-37598-3 Text en © Crown 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Das, Nabangshu
de Almeida, Luiz G. N.
Derakhshani, Afshin
Young, Daniel
Mehdinejadiani, Kobra
Salo, Paul
Rezansoff, Alexander
Jay, Gregory D.
Sommerhoff, Christian P.
Schmidt, Tannin A.
Krawetz, Roman
Dufour, Antoine
Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title_full Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title_fullStr Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title_full_unstemmed Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title_short Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
title_sort tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079686/
https://www.ncbi.nlm.nih.gov/pubmed/37024468
http://dx.doi.org/10.1038/s41467-023-37598-3
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