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The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage
OBJECTIVE: We sought to determine whether follistatin‐like protein 1 (FSTL1), a protein produced by articular chondrocytes, promotes healthy articular cartilage and prevents chondrocytes from undergoing terminal differentiation to hypertrophic cells. METHODS: In vitro experiments were performed with...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368136/ https://www.ncbi.nlm.nih.gov/pubmed/32530126 http://dx.doi.org/10.1002/acr2.11155 |
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author | Chaly, Yury Hostager, Bruce Smith, Sonja Hirsch, Raphael |
author_facet | Chaly, Yury Hostager, Bruce Smith, Sonja Hirsch, Raphael |
author_sort | Chaly, Yury |
collection | PubMed |
description | OBJECTIVE: We sought to determine whether follistatin‐like protein 1 (FSTL1), a protein produced by articular chondrocytes, promotes healthy articular cartilage and prevents chondrocytes from undergoing terminal differentiation to hypertrophic cells. METHODS: In vitro experiments were performed with immortalized human articular chondrocytes. The cells were transduced with a lentivirus encoding human FSTL1 small hairpin RNA or with an adenovirus encoding FSTL1. A quantitative polymerase chain reaction was used for gene expression analysis. Protein expression was assessed by Western blotting. Co‐immunoprecipitation was used to identify interacting partners of FSTL1. FSTL1 expression in human articular cartilage was analyzed using confocal microscopy. RESULTS: Downregulation of FSTL1 expression in transforming growth factor β (TGFβ)‐stimulated chondrocyte pellet cultures led to chondrocyte terminal differentiation characterized by poor production of cartilage extracellular matrix and altered expression of genes and proteins involved in cartilage homeostasis, including MMP13, COL10A1, RUNX2, COL2A1, ACAN, Sox9, and phospho‐Smad3. We also showed that FSTL1 interacts with TGFβ receptor proteins, Alk1 and endoglin, suggesting a potential mechanism for its effects on chondrocytes. Transduction of chondrocytes with an FSTL1 transgene increased COL2A1 expression, whereas it did not affect MMP13 expression. FSTL1 protein expression was decreased in human osteoarthritic cartilage in situ. CONCLUSION: Our data suggest that FSTL1 plays an important role in maintaining healthy articular cartilage and the FSTL1 pathway may represent a therapeutic target for degenerative diseases of cartilage. |
format | Online Article Text |
id | pubmed-7368136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73681362020-07-20 The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage Chaly, Yury Hostager, Bruce Smith, Sonja Hirsch, Raphael ACR Open Rheumatol Original Articles OBJECTIVE: We sought to determine whether follistatin‐like protein 1 (FSTL1), a protein produced by articular chondrocytes, promotes healthy articular cartilage and prevents chondrocytes from undergoing terminal differentiation to hypertrophic cells. METHODS: In vitro experiments were performed with immortalized human articular chondrocytes. The cells were transduced with a lentivirus encoding human FSTL1 small hairpin RNA or with an adenovirus encoding FSTL1. A quantitative polymerase chain reaction was used for gene expression analysis. Protein expression was assessed by Western blotting. Co‐immunoprecipitation was used to identify interacting partners of FSTL1. FSTL1 expression in human articular cartilage was analyzed using confocal microscopy. RESULTS: Downregulation of FSTL1 expression in transforming growth factor β (TGFβ)‐stimulated chondrocyte pellet cultures led to chondrocyte terminal differentiation characterized by poor production of cartilage extracellular matrix and altered expression of genes and proteins involved in cartilage homeostasis, including MMP13, COL10A1, RUNX2, COL2A1, ACAN, Sox9, and phospho‐Smad3. We also showed that FSTL1 interacts with TGFβ receptor proteins, Alk1 and endoglin, suggesting a potential mechanism for its effects on chondrocytes. Transduction of chondrocytes with an FSTL1 transgene increased COL2A1 expression, whereas it did not affect MMP13 expression. FSTL1 protein expression was decreased in human osteoarthritic cartilage in situ. CONCLUSION: Our data suggest that FSTL1 plays an important role in maintaining healthy articular cartilage and the FSTL1 pathway may represent a therapeutic target for degenerative diseases of cartilage. John Wiley and Sons Inc. 2020-06-12 /pmc/articles/PMC7368136/ /pubmed/32530126 http://dx.doi.org/10.1002/acr2.11155 Text en © 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Chaly, Yury Hostager, Bruce Smith, Sonja Hirsch, Raphael The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title | The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title_full | The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title_fullStr | The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title_full_unstemmed | The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title_short | The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage |
title_sort | follistatin‐like protein 1 pathway is important for maintaining healthy articular cartilage |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368136/ https://www.ncbi.nlm.nih.gov/pubmed/32530126 http://dx.doi.org/10.1002/acr2.11155 |
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