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The potential role of protease systems in hemophilic arthropathy

Hemophilic arthropathy (HA) is characterized by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder hemophilia. Joint bleeds or hemarthroses trigger inflammation in the synovial tissue, which promotes damage to the articular cartilage. The...

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Autores principales: Hauw, Wayne W. S., Chia, Joanne S. J., Nandurkar, Harshal H., Sashindranath, Maithili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631709/
https://www.ncbi.nlm.nih.gov/pubmed/35580335
http://dx.doi.org/10.1182/bloodadvances.2022007028
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author Hauw, Wayne W. S.
Chia, Joanne S. J.
Nandurkar, Harshal H.
Sashindranath, Maithili
author_facet Hauw, Wayne W. S.
Chia, Joanne S. J.
Nandurkar, Harshal H.
Sashindranath, Maithili
author_sort Hauw, Wayne W. S.
collection PubMed
description Hemophilic arthropathy (HA) is characterized by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder hemophilia. Joint bleeds or hemarthroses trigger inflammation in the synovial tissue, which promotes damage to the articular cartilage. The plasminogen activation system is integral to fibrinolysis, and the urokinase plasminogen activator, or uPA in particular, is strongly upregulated following hemarthroses. uPA is a serine protease that catalyzes the production of plasmin, a broad-spectrum protease that can degrade fibrin as well as proteins of the joint extracellular matrix and cartilage. Both uPA and plasmin are able to proteolytically generate active forms of matrix metalloproteinases (MMPs). The MMPs are a family of >20 proteases that are secreted as inactive proenzymes and are activated extracellularly. MMPs are involved in the degradation of all types of collagen and proteoglycans that constitute the extracellular matrix, which provides structural support to articular cartilage. The MMPs have an established role in joint destruction following rheumatoid arthritis (RA). They degrade cartilage and bone, indirectly promoting angiogenesis. MMPs are also implicated in the pathology of osteoarthritis (OA), characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce the comorbidity of hemophilia.
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spelling pubmed-96317092022-11-04 The potential role of protease systems in hemophilic arthropathy Hauw, Wayne W. S. Chia, Joanne S. J. Nandurkar, Harshal H. Sashindranath, Maithili Blood Adv Review Article Hemophilic arthropathy (HA) is characterized by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder hemophilia. Joint bleeds or hemarthroses trigger inflammation in the synovial tissue, which promotes damage to the articular cartilage. The plasminogen activation system is integral to fibrinolysis, and the urokinase plasminogen activator, or uPA in particular, is strongly upregulated following hemarthroses. uPA is a serine protease that catalyzes the production of plasmin, a broad-spectrum protease that can degrade fibrin as well as proteins of the joint extracellular matrix and cartilage. Both uPA and plasmin are able to proteolytically generate active forms of matrix metalloproteinases (MMPs). The MMPs are a family of >20 proteases that are secreted as inactive proenzymes and are activated extracellularly. MMPs are involved in the degradation of all types of collagen and proteoglycans that constitute the extracellular matrix, which provides structural support to articular cartilage. The MMPs have an established role in joint destruction following rheumatoid arthritis (RA). They degrade cartilage and bone, indirectly promoting angiogenesis. MMPs are also implicated in the pathology of osteoarthritis (OA), characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce the comorbidity of hemophilia. American Society of Hematology 2022-09-27 /pmc/articles/PMC9631709/ /pubmed/35580335 http://dx.doi.org/10.1182/bloodadvances.2022007028 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
spellingShingle Review Article
Hauw, Wayne W. S.
Chia, Joanne S. J.
Nandurkar, Harshal H.
Sashindranath, Maithili
The potential role of protease systems in hemophilic arthropathy
title The potential role of protease systems in hemophilic arthropathy
title_full The potential role of protease systems in hemophilic arthropathy
title_fullStr The potential role of protease systems in hemophilic arthropathy
title_full_unstemmed The potential role of protease systems in hemophilic arthropathy
title_short The potential role of protease systems in hemophilic arthropathy
title_sort potential role of protease systems in hemophilic arthropathy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631709/
https://www.ncbi.nlm.nih.gov/pubmed/35580335
http://dx.doi.org/10.1182/bloodadvances.2022007028
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