Cargando…
Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray
Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subc...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288107/ https://www.ncbi.nlm.nih.gov/pubmed/22384228 http://dx.doi.org/10.1371/journal.pone.0032356 |
_version_ | 1782224806919274496 |
---|---|
author | Zhang, RongKai Fang, Hang Chen, YuXian Shen, Jun Lu, HuaDing Zeng, Chun Ren, JianHua Zeng, Hua Li, ZhiFu Chen, ShaoMing Cai, DaoZhang Zhao, Qing |
author_facet | Zhang, RongKai Fang, Hang Chen, YuXian Shen, Jun Lu, HuaDing Zeng, Chun Ren, JianHua Zeng, Hua Li, ZhiFu Chen, ShaoMing Cai, DaoZhang Zhao, Qing |
author_sort | Zhang, RongKai |
collection | PubMed |
description | Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf β1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA. |
format | Online Article Text |
id | pubmed-3288107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32881072012-03-01 Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray Zhang, RongKai Fang, Hang Chen, YuXian Shen, Jun Lu, HuaDing Zeng, Chun Ren, JianHua Zeng, Hua Li, ZhiFu Chen, ShaoMing Cai, DaoZhang Zhao, Qing PLoS One Research Article Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf β1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA. Public Library of Science 2012-02-27 /pmc/articles/PMC3288107/ /pubmed/22384228 http://dx.doi.org/10.1371/journal.pone.0032356 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, RongKai Fang, Hang Chen, YuXian Shen, Jun Lu, HuaDing Zeng, Chun Ren, JianHua Zeng, Hua Li, ZhiFu Chen, ShaoMing Cai, DaoZhang Zhao, Qing Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title | Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title_full | Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title_fullStr | Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title_full_unstemmed | Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title_short | Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray |
title_sort | gene expression analyses of subchondral bone in early experimental osteoarthritis by microarray |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288107/ https://www.ncbi.nlm.nih.gov/pubmed/22384228 http://dx.doi.org/10.1371/journal.pone.0032356 |
work_keys_str_mv | AT zhangrongkai geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT fanghang geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT chenyuxian geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT shenjun geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT luhuading geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT zengchun geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT renjianhua geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT zenghua geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT lizhifu geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT chenshaoming geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT caidaozhang geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray AT zhaoqing geneexpressionanalysesofsubchondralboneinearlyexperimentalosteoarthritisbymicroarray |