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L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis

Osteoarthritis (OA) is the most common musculoskeletal disorder among the elderly. It is characterized by progressive cartilage degradation, synovial inflammation, subchondral bone remodeling and pain. Lipocalin prostaglandin D synthase (L-PGDS) is responsible for the biosynthesis of PGD(2), which h...

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Autores principales: Ouhaddi, Yassine, Najar, Mehdi, Paré, Frédéric, Lussier, Bertrand, Urade, Yoshihiro, Benderdour, Mohamed, Pelletier, Jean-Pierre, Martel-Pelletier, Johanne, Fahmi, Hassan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803483/
https://www.ncbi.nlm.nih.gov/pubmed/33361529
http://dx.doi.org/10.18632/aging.202367
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author Ouhaddi, Yassine
Najar, Mehdi
Paré, Frédéric
Lussier, Bertrand
Urade, Yoshihiro
Benderdour, Mohamed
Pelletier, Jean-Pierre
Martel-Pelletier, Johanne
Fahmi, Hassan
author_facet Ouhaddi, Yassine
Najar, Mehdi
Paré, Frédéric
Lussier, Bertrand
Urade, Yoshihiro
Benderdour, Mohamed
Pelletier, Jean-Pierre
Martel-Pelletier, Johanne
Fahmi, Hassan
author_sort Ouhaddi, Yassine
collection PubMed
description Osteoarthritis (OA) is the most common musculoskeletal disorder among the elderly. It is characterized by progressive cartilage degradation, synovial inflammation, subchondral bone remodeling and pain. Lipocalin prostaglandin D synthase (L-PGDS) is responsible for the biosynthesis of PGD(2), which has been implicated in the regulation of inflammation and cartilage biology. This study aimed to evaluate the effect of L-PGDS deficiency on the development of naturally occurring age-related OA in mice. OA-like structural changes were assessed by histology, immunohistochemistry, and micro–computed tomography. Pain related behaviours were assessed using the von Frey and the open-field assays. L-PGDS deletion promoted cartilage degradation during aging, which was associated with enhanced expression of extracellular matrix degrading enzymes, matrix metalloprotease 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and their breakdown products, C1,2C, VDIPEN and NITEG. Moreover, L-PGDS deletion enhanced subchondral bone changes, but had no effect on its angiogenesis. Additionally, L-PGDS deletion increased mechanical sensitivity and reduced spontaneous locomotor activity. Finally, we showed that the expression of L-PGDS was elevated in aged mice. Together, these findings indicate an important role for L-PGDS in naturally occurring age-related OA. They also suggest that L-PGDS may constitute a new efficient therapeutic target in OA.
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spelling pubmed-78034832021-01-15 L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis Ouhaddi, Yassine Najar, Mehdi Paré, Frédéric Lussier, Bertrand Urade, Yoshihiro Benderdour, Mohamed Pelletier, Jean-Pierre Martel-Pelletier, Johanne Fahmi, Hassan Aging (Albany NY) Research Paper Osteoarthritis (OA) is the most common musculoskeletal disorder among the elderly. It is characterized by progressive cartilage degradation, synovial inflammation, subchondral bone remodeling and pain. Lipocalin prostaglandin D synthase (L-PGDS) is responsible for the biosynthesis of PGD(2), which has been implicated in the regulation of inflammation and cartilage biology. This study aimed to evaluate the effect of L-PGDS deficiency on the development of naturally occurring age-related OA in mice. OA-like structural changes were assessed by histology, immunohistochemistry, and micro–computed tomography. Pain related behaviours were assessed using the von Frey and the open-field assays. L-PGDS deletion promoted cartilage degradation during aging, which was associated with enhanced expression of extracellular matrix degrading enzymes, matrix metalloprotease 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and their breakdown products, C1,2C, VDIPEN and NITEG. Moreover, L-PGDS deletion enhanced subchondral bone changes, but had no effect on its angiogenesis. Additionally, L-PGDS deletion increased mechanical sensitivity and reduced spontaneous locomotor activity. Finally, we showed that the expression of L-PGDS was elevated in aged mice. Together, these findings indicate an important role for L-PGDS in naturally occurring age-related OA. They also suggest that L-PGDS may constitute a new efficient therapeutic target in OA. Impact Journals 2020-12-23 /pmc/articles/PMC7803483/ /pubmed/33361529 http://dx.doi.org/10.18632/aging.202367 Text en Copyright: © 2020 Ouhaddi et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ouhaddi, Yassine
Najar, Mehdi
Paré, Frédéric
Lussier, Bertrand
Urade, Yoshihiro
Benderdour, Mohamed
Pelletier, Jean-Pierre
Martel-Pelletier, Johanne
Fahmi, Hassan
L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title_full L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title_fullStr L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title_full_unstemmed L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title_short L-PGDS deficiency accelerated the development of naturally occurring age-related osteoarthritis
title_sort l-pgds deficiency accelerated the development of naturally occurring age-related osteoarthritis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803483/
https://www.ncbi.nlm.nih.gov/pubmed/33361529
http://dx.doi.org/10.18632/aging.202367
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