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Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity
Aggrecan is a critical component of the extracellular matrix of all cartilages. One of the early hallmarks of osteoarthritis (OA) is the loss of aggrecan from articular cartilage followed by degeneration of the tissue. Mesenchymal progenitor cell (MPC) populations in joints, including those in the s...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117284/ https://www.ncbi.nlm.nih.gov/pubmed/35585042 http://dx.doi.org/10.1038/s41419-022-04919-1 |
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author | Krawetz, Roman J. Wu, Yiru Elizabeth Bertram, Karri L. Shonak, Anchita Masson, Anand O. Ren, Guomin Leonard, Catherine Kapoor, Mohit Matyas, John R. Salo, Paul T. |
author_facet | Krawetz, Roman J. Wu, Yiru Elizabeth Bertram, Karri L. Shonak, Anchita Masson, Anand O. Ren, Guomin Leonard, Catherine Kapoor, Mohit Matyas, John R. Salo, Paul T. |
author_sort | Krawetz, Roman J. |
collection | PubMed |
description | Aggrecan is a critical component of the extracellular matrix of all cartilages. One of the early hallmarks of osteoarthritis (OA) is the loss of aggrecan from articular cartilage followed by degeneration of the tissue. Mesenchymal progenitor cell (MPC) populations in joints, including those in the synovium, have been hypothesized to play a role in the maintenance and/or repair of cartilage, however, the mechanism by which this may occur is unknown. In the current study, we have uncovered that aggrecan is secreted by synovial MPCs from healthy joints yet accumulates inside synovial MPCs within OA joints. Using human synovial biopsies and a rat model of OA, we established that this observation in aggrecan metabolism also occurs in vivo. Moreover, the loss of the “anti-proteinase” molecule alpha-2 macroglobulin (A2M) inhibits aggrecan secretion in OA synovial MPCs, whereas overexpressing A2M rescues the normal secretion of aggrecan. Using mice models of OA and cartilage repair, we have demonstrated that intra-articular injection of aggrecan into OA joints inhibits cartilage degeneration and stimulates cartilage repair respectively. Furthermore, when synovial MPCs overexpressing aggrecan were transplanted into injured joints, increased cartilage regeneration was observed vs. wild-type MPCs or MPCs with diminished aggrecan expression. Overall, these results suggest that aggrecan secreted from joint-associated MPCs may play a role in tissue homeostasis and repair of synovial joints. |
format | Online Article Text |
id | pubmed-9117284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91172842022-05-20 Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity Krawetz, Roman J. Wu, Yiru Elizabeth Bertram, Karri L. Shonak, Anchita Masson, Anand O. Ren, Guomin Leonard, Catherine Kapoor, Mohit Matyas, John R. Salo, Paul T. Cell Death Dis Article Aggrecan is a critical component of the extracellular matrix of all cartilages. One of the early hallmarks of osteoarthritis (OA) is the loss of aggrecan from articular cartilage followed by degeneration of the tissue. Mesenchymal progenitor cell (MPC) populations in joints, including those in the synovium, have been hypothesized to play a role in the maintenance and/or repair of cartilage, however, the mechanism by which this may occur is unknown. In the current study, we have uncovered that aggrecan is secreted by synovial MPCs from healthy joints yet accumulates inside synovial MPCs within OA joints. Using human synovial biopsies and a rat model of OA, we established that this observation in aggrecan metabolism also occurs in vivo. Moreover, the loss of the “anti-proteinase” molecule alpha-2 macroglobulin (A2M) inhibits aggrecan secretion in OA synovial MPCs, whereas overexpressing A2M rescues the normal secretion of aggrecan. Using mice models of OA and cartilage repair, we have demonstrated that intra-articular injection of aggrecan into OA joints inhibits cartilage degeneration and stimulates cartilage repair respectively. Furthermore, when synovial MPCs overexpressing aggrecan were transplanted into injured joints, increased cartilage regeneration was observed vs. wild-type MPCs or MPCs with diminished aggrecan expression. Overall, these results suggest that aggrecan secreted from joint-associated MPCs may play a role in tissue homeostasis and repair of synovial joints. Nature Publishing Group UK 2022-05-18 /pmc/articles/PMC9117284/ /pubmed/35585042 http://dx.doi.org/10.1038/s41419-022-04919-1 Text en © The Author(s) 2022 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 Krawetz, Roman J. Wu, Yiru Elizabeth Bertram, Karri L. Shonak, Anchita Masson, Anand O. Ren, Guomin Leonard, Catherine Kapoor, Mohit Matyas, John R. Salo, Paul T. Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title | Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title_full | Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title_fullStr | Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title_full_unstemmed | Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title_short | Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
title_sort | synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117284/ https://www.ncbi.nlm.nih.gov/pubmed/35585042 http://dx.doi.org/10.1038/s41419-022-04919-1 |
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