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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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