Cargando…
OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes
OBJECTIVES: A recent work has reported that the elevated osteopontin (OPN) levels in the articular cartilage and synovial fluid are correlated with the progressive osteoarthritis (OA) joint damage, and OPN has a protective effect against OA by suppressing the expressions of OA-associated genes. The...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599390/ https://www.ncbi.nlm.nih.gov/pubmed/33144900 http://dx.doi.org/10.1155/2020/3428587 |
_version_ | 1783602860736380928 |
---|---|
author | Tian, Jian Cheng, Chao Kuang, Shi-Da Su, Chao Zhao, Xin Xiong, Yi-lin Li, Yu-Sheng Gao, Shu-Guang |
author_facet | Tian, Jian Cheng, Chao Kuang, Shi-Da Su, Chao Zhao, Xin Xiong, Yi-lin Li, Yu-Sheng Gao, Shu-Guang |
author_sort | Tian, Jian |
collection | PubMed |
description | OBJECTIVES: A recent work has reported that the elevated osteopontin (OPN) levels in the articular cartilage and synovial fluid are correlated with the progressive osteoarthritis (OA) joint damage, and OPN has a protective effect against OA by suppressing the expressions of OA-associated genes. The present study examined whether the OPN deficiency was susceptible to OA through the regulation of chondrocyte senescence and apoptosis and the expressions of OA-associated genes. METHODS: The mRNA levels of COL2A1 and OPN were compared between human OA chondrocytes and normal chondrocytes. The effects of OPN siRNA on the SA-β-Gal expressions and the percentage of apoptotic chondrocytes were examined by using SA-β-Gal staining and apoptosis assay, and the effects on the expressions of COL2A1 and OA-associated genes (COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5) were examined by western blot analysis and quantitative real-time RT-PCR. Furthermore, an in vivo OA model was established to examine the effects of OPN siRNA on the senescence and apoptosis of OA chondrocytes and the expressions of OA-associated genes. RESULTS: The mRNA levels of COL2A1 and OPN were decreased in knee OA chondrocytes in comparison with those in normal chondrocytes. The OPN deficiency enhanced the senescence and apoptosis of OA chondrocytes and increased the expressions of COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5 but decreased the expression of COL2A1. Meanwhile, OPN deficiency could result in severe, accelerated OA in vivo, which was also associated with enhanced senescence and apoptosis of chondrocytes and elevated expressions of OA-associated genes. CONCLUSIONS: The findings of this study suggest that the OPN deficiency can result in accelerated OA, which is associated with enhanced senescence and apoptosis of OA chondrocytes and the upregulated expressions of OA-associated genes. |
format | Online Article Text |
id | pubmed-7599390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-75993902020-11-02 OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes Tian, Jian Cheng, Chao Kuang, Shi-Da Su, Chao Zhao, Xin Xiong, Yi-lin Li, Yu-Sheng Gao, Shu-Guang Pain Res Manag Research Article OBJECTIVES: A recent work has reported that the elevated osteopontin (OPN) levels in the articular cartilage and synovial fluid are correlated with the progressive osteoarthritis (OA) joint damage, and OPN has a protective effect against OA by suppressing the expressions of OA-associated genes. The present study examined whether the OPN deficiency was susceptible to OA through the regulation of chondrocyte senescence and apoptosis and the expressions of OA-associated genes. METHODS: The mRNA levels of COL2A1 and OPN were compared between human OA chondrocytes and normal chondrocytes. The effects of OPN siRNA on the SA-β-Gal expressions and the percentage of apoptotic chondrocytes were examined by using SA-β-Gal staining and apoptosis assay, and the effects on the expressions of COL2A1 and OA-associated genes (COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5) were examined by western blot analysis and quantitative real-time RT-PCR. Furthermore, an in vivo OA model was established to examine the effects of OPN siRNA on the senescence and apoptosis of OA chondrocytes and the expressions of OA-associated genes. RESULTS: The mRNA levels of COL2A1 and OPN were decreased in knee OA chondrocytes in comparison with those in normal chondrocytes. The OPN deficiency enhanced the senescence and apoptosis of OA chondrocytes and increased the expressions of COL10A1, IL-1β, TNF-ɑ, MMP-13, and ADAMTS5 but decreased the expression of COL2A1. Meanwhile, OPN deficiency could result in severe, accelerated OA in vivo, which was also associated with enhanced senescence and apoptosis of chondrocytes and elevated expressions of OA-associated genes. CONCLUSIONS: The findings of this study suggest that the OPN deficiency can result in accelerated OA, which is associated with enhanced senescence and apoptosis of OA chondrocytes and the upregulated expressions of OA-associated genes. Hindawi 2020-10-22 /pmc/articles/PMC7599390/ /pubmed/33144900 http://dx.doi.org/10.1155/2020/3428587 Text en Copyright © 2020 Jian Tian et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tian, Jian Cheng, Chao Kuang, Shi-Da Su, Chao Zhao, Xin Xiong, Yi-lin Li, Yu-Sheng Gao, Shu-Guang OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title | OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title_full | OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title_fullStr | OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title_full_unstemmed | OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title_short | OPN Deficiency Increases the Severity of Osteoarthritis Associated with Aberrant Chondrocyte Senescence and Apoptosis and Upregulates the Expression of Osteoarthritis-Associated Genes |
title_sort | opn deficiency increases the severity of osteoarthritis associated with aberrant chondrocyte senescence and apoptosis and upregulates the expression of osteoarthritis-associated genes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599390/ https://www.ncbi.nlm.nih.gov/pubmed/33144900 http://dx.doi.org/10.1155/2020/3428587 |
work_keys_str_mv | AT tianjian opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT chengchao opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT kuangshida opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT suchao opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT zhaoxin opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT xiongyilin opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT liyusheng opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes AT gaoshuguang opndeficiencyincreasestheseverityofosteoarthritisassociatedwithaberrantchondrocytesenescenceandapoptosisandupregulatestheexpressionofosteoarthritisassociatedgenes |