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miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro
Interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and WNT/β‐catenin signaling cause dysregulation of rat primary articular chondrocytes (rArCs), resulting in cartilage extracellular matrix destruction and osteoarthritis (OA) progression. microRNA (miR) miR‐122 represses these effects whereas...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320820/ https://www.ncbi.nlm.nih.gov/pubmed/35362116 http://dx.doi.org/10.1002/jcb.30244 |
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author | Scott, Kayla M. Cohen, D. Joshua Boyan, Barbara D. Schwartz, Zvi |
author_facet | Scott, Kayla M. Cohen, D. Joshua Boyan, Barbara D. Schwartz, Zvi |
author_sort | Scott, Kayla M. |
collection | PubMed |
description | Interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and WNT/β‐catenin signaling cause dysregulation of rat primary articular chondrocytes (rArCs), resulting in cartilage extracellular matrix destruction and osteoarthritis (OA) progression. microRNA (miR) miR‐122 represses these effects whereas miR‐451 exacerbates IL‐1β‐stimulated matrix metalloproteinase‐13 (MMP‐13) and prostaglandin E2 (PGE2) production. The goals of this study were to evaluate crosstalk between these signaling pathways and determine if miR‐122 and miR‐451 exert their protective/destructive effects through these pathways in an in vitro model of OA. Primary rArCs were treated with IL‐1β or TNF‐α for 24 h and total DNA, MMP‐13, and PGE2, as well as expression levels of miR‐122 and miR‐451 were measured. After 24‐h transfection with miR‐122, miR‐451, miR‐122‐inhibitor, or miR‐451‐inhibitor, rArCs were treated with or without TNF‐α for 24 h; total DNA, MMP‐13, and PGE2 were measured. Similarly, cells were treated with WNT‐agonist lithium chloride (LiCl), WNT‐antagonist XAV‐939 (XAV), or PKF‐118‐310 (PKF) with and without IL‐1β or TNF‐α stimulation. Both IL‐1β and TNF‐α‐stimulation increased MMP‐13 and PGE2 production. Transfection with miR‐122 prevented TNF‐α‐stimulated increases in MMP‐13 and PGE2 whereas transfection with miR‐451 did not change these levels. No differences were found in MMP‐13 or PGE2 production with miR‐122 or miR‐451 inhibitors. LiCl treatment decreased PGE2 production in cultures treated with TNF‐α, but not MMP‐13. XAV increased TNF‐α‐stimulated increases in PGE2 but not MMP‐13. LiCl reduced IL‐1β‐stimulated increases in MMP‐13 and PGE2. XAV and PKF increased IL‐1β‐stimulated increases in MMP‐13 and PGE2. In this in vitro OA model, miR‐122 protects against both IL‐1β and TNF‐α stimulated increases in MMP‐13 and PGE2 production. miR‐451 does not act through the TNF‐α pathway. The WNT/β‐catenin pathway regulates the effects of IL‐1β and TNF‐α stimulation. This study suggests that miR‐122 can be used as a treatment or prevention for OA. |
format | Online Article Text |
id | pubmed-9320820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93208202022-07-30 miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro Scott, Kayla M. Cohen, D. Joshua Boyan, Barbara D. Schwartz, Zvi J Cell Biochem Research Articles Interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and WNT/β‐catenin signaling cause dysregulation of rat primary articular chondrocytes (rArCs), resulting in cartilage extracellular matrix destruction and osteoarthritis (OA) progression. microRNA (miR) miR‐122 represses these effects whereas miR‐451 exacerbates IL‐1β‐stimulated matrix metalloproteinase‐13 (MMP‐13) and prostaglandin E2 (PGE2) production. The goals of this study were to evaluate crosstalk between these signaling pathways and determine if miR‐122 and miR‐451 exert their protective/destructive effects through these pathways in an in vitro model of OA. Primary rArCs were treated with IL‐1β or TNF‐α for 24 h and total DNA, MMP‐13, and PGE2, as well as expression levels of miR‐122 and miR‐451 were measured. After 24‐h transfection with miR‐122, miR‐451, miR‐122‐inhibitor, or miR‐451‐inhibitor, rArCs were treated with or without TNF‐α for 24 h; total DNA, MMP‐13, and PGE2 were measured. Similarly, cells were treated with WNT‐agonist lithium chloride (LiCl), WNT‐antagonist XAV‐939 (XAV), or PKF‐118‐310 (PKF) with and without IL‐1β or TNF‐α stimulation. Both IL‐1β and TNF‐α‐stimulation increased MMP‐13 and PGE2 production. Transfection with miR‐122 prevented TNF‐α‐stimulated increases in MMP‐13 and PGE2 whereas transfection with miR‐451 did not change these levels. No differences were found in MMP‐13 or PGE2 production with miR‐122 or miR‐451 inhibitors. LiCl treatment decreased PGE2 production in cultures treated with TNF‐α, but not MMP‐13. XAV increased TNF‐α‐stimulated increases in PGE2 but not MMP‐13. LiCl reduced IL‐1β‐stimulated increases in MMP‐13 and PGE2. XAV and PKF increased IL‐1β‐stimulated increases in MMP‐13 and PGE2. In this in vitro OA model, miR‐122 protects against both IL‐1β and TNF‐α stimulated increases in MMP‐13 and PGE2 production. miR‐451 does not act through the TNF‐α pathway. The WNT/β‐catenin pathway regulates the effects of IL‐1β and TNF‐α stimulation. This study suggests that miR‐122 can be used as a treatment or prevention for OA. John Wiley and Sons Inc. 2022-03-31 2022-06 /pmc/articles/PMC9320820/ /pubmed/35362116 http://dx.doi.org/10.1002/jcb.30244 Text en © 2022 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Scott, Kayla M. Cohen, D. Joshua Boyan, Barbara D. Schwartz, Zvi miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title | miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title_full | miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title_fullStr | miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title_full_unstemmed | miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title_short | miR‐122 and the WNT/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
title_sort | mir‐122 and the wnt/β‐catenin pathway inhibit effects of both interleukin‐1β and tumor necrosis factor‐α in articular chondrocytes in vitro |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320820/ https://www.ncbi.nlm.nih.gov/pubmed/35362116 http://dx.doi.org/10.1002/jcb.30244 |
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