Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia

Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage...

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Autores principales: Hernandez, Paula A., Wells, Joel, Usheva, Emiliya, Nakonezny, Paul A., Barati, Zahra, Gonzalez, Roberto, Kassem, Layla, Henson, Frances M. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969105/
https://www.ncbi.nlm.nih.gov/pubmed/31953438
http://dx.doi.org/10.1038/s41598-020-57431-x
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author Hernandez, Paula A.
Wells, Joel
Usheva, Emiliya
Nakonezny, Paul A.
Barati, Zahra
Gonzalez, Roberto
Kassem, Layla
Henson, Frances M. D.
author_facet Hernandez, Paula A.
Wells, Joel
Usheva, Emiliya
Nakonezny, Paul A.
Barati, Zahra
Gonzalez, Roberto
Kassem, Layla
Henson, Frances M. D.
author_sort Hernandez, Paula A.
collection PubMed
description Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α(5)β(1), (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA.
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spelling pubmed-69691052020-01-22 Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia Hernandez, Paula A. Wells, Joel Usheva, Emiliya Nakonezny, Paul A. Barati, Zahra Gonzalez, Roberto Kassem, Layla Henson, Frances M. D. Sci Rep Article Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α(5)β(1), (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA. Nature Publishing Group UK 2020-01-17 /pmc/articles/PMC6969105/ /pubmed/31953438 http://dx.doi.org/10.1038/s41598-020-57431-x Text en © The Author(s) 2020 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/.
spellingShingle Article
Hernandez, Paula A.
Wells, Joel
Usheva, Emiliya
Nakonezny, Paul A.
Barati, Zahra
Gonzalez, Roberto
Kassem, Layla
Henson, Frances M. D.
Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title_full Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title_fullStr Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title_full_unstemmed Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title_short Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
title_sort early-onset osteoarthritis originates at the chondrocyte level in hip dysplasia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969105/
https://www.ncbi.nlm.nih.gov/pubmed/31953438
http://dx.doi.org/10.1038/s41598-020-57431-x
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