Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy
Objectives:To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.Methods:Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were com...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2010-01, Vol.69 (1), p.234-240 |
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| creator | Brew, C J Clegg, P D Boot-Handford, R P Andrew, J G Hardingham, T |
| description | Objectives:To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.Methods:Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.Results:There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p |
| doi_str_mv | 10.1136/ard.2008.097139 |
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Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.Results:There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).Conclusions:The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.]]></description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/ard.2008.097139</identifier><identifier>PMID: 19103633</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><subject>Age ; Aged ; Aged, 80 and over ; Aggrecans - biosynthesis ; Aggrecans - genetics ; Arthritis ; Cartilage, Articular - metabolism ; Cartilage, Articular - pathology ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Collagen ; Collagen - biosynthesis ; Collagen - genetics ; Female ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation ; Histology ; Humans ; Hypertrophy - genetics ; Hypertrophy - metabolism ; Joint surgery ; Knee Joint - physiopathology ; Male ; Middle Aged ; Osteoarthritis, Knee - genetics ; Osteoarthritis, Knee - metabolism ; Osteoarthritis, Knee - pathology ; Principal components analysis ; RNA, Messenger - genetics ; SOX9 Transcription Factor - biosynthesis ; SOX9 Transcription Factor - genetics ; Standard scores ; Weight-Bearing</subject><ispartof>Annals of the rheumatic diseases, 2010-01, Vol.69 (1), p.234-240</ispartof><rights>BMJ Publishing Group Ltd and European League Against Rheumatism. All rights reserved.</rights><rights>Copyright: 2010 BMJ Publishing Group Ltd and European League Against Rheumatism. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b397t-4d6cf05cb79d9f380950651375823fd6b816c8e978891951e4aaaf8597eb16e43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/69/01/234.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/69/01/234.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3195,23570,27923,27924,77471,77502</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19103633$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brew, C J</creatorcontrib><creatorcontrib>Clegg, P D</creatorcontrib><creatorcontrib>Boot-Handford, R P</creatorcontrib><creatorcontrib>Andrew, J G</creatorcontrib><creatorcontrib>Hardingham, T</creatorcontrib><title>Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description><![CDATA[Objectives:To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.Methods:Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.Results:There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).Conclusions:The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.]]></description><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aggrecans - biosynthesis</subject><subject>Aggrecans - genetics</subject><subject>Arthritis</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cartilage, Articular - pathology</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrocytes - pathology</subject><subject>Collagen</subject><subject>Collagen - biosynthesis</subject><subject>Collagen - genetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation</subject><subject>Histology</subject><subject>Humans</subject><subject>Hypertrophy - genetics</subject><subject>Hypertrophy - metabolism</subject><subject>Joint surgery</subject><subject>Knee Joint - physiopathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Osteoarthritis, Knee - genetics</subject><subject>Osteoarthritis, Knee - metabolism</subject><subject>Osteoarthritis, Knee - pathology</subject><subject>Principal components analysis</subject><subject>RNA, Messenger - genetics</subject><subject>SOX9 Transcription Factor - biosynthesis</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>Standard scores</subject><subject>Weight-Bearing</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU-P0zAQxSMEYsvCmRuyxAEJKV07TvznyFawILqABKy4WU4yaVxSO9gObL8RHxNHqQBx4WR55vfmzehl2WOC14RQdqF9uy4wFmssOaHyTrYiJRN5gRm-m60wxjQvJeNn2YMQ9umLBRH3szMiCaaM0lX28wosILgdPYRgnEXGon46aIua3tnWu-YYIczVQUdALkRw2sfem2hSOSRM2x20M1G72KPO1N4MM9wibed61E1ETRKZQe8A_TCxd1NE8N20YJs0s0O7tITXgwlJ9Jcv6o8j-Ojd2B8fZvc6PQR4dHrPs8-vXn7avM6376_ebF5s85pKHvOyZU2Hq6bmspUdFVhWmFWE8koUtGtZLQhrBEguhCSyIlBqrTtRSQ41YVDS8-zZMnf07tsEIaqDCQ2kiyy4KShOSyILynEin_5D7t3kbVpOEc65SI6kSNTFQjXeheChU6M3B-2PimA1Z6hShmrOUC0ZJsWT09ypPkD7hz-FloB8AUxK4_Z3X_uvivF0qXp3s1GXbz98uf64vVY3iX--8PVh_1_3X8DPt6c</recordid><startdate>201001</startdate><enddate>201001</enddate><creator>Brew, C J</creator><creator>Clegg, P D</creator><creator>Boot-Handford, R P</creator><creator>Andrew, J G</creator><creator>Hardingham, T</creator><general>BMJ Publishing Group Ltd and European League Against Rheumatism</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>201001</creationdate><title>Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy</title><author>Brew, C J ; Clegg, P D ; Boot-Handford, R P ; Andrew, J G ; Hardingham, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b397t-4d6cf05cb79d9f380950651375823fd6b816c8e978891951e4aaaf8597eb16e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aggrecans - biosynthesis</topic><topic>Aggrecans - genetics</topic><topic>Arthritis</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cartilage, Articular - pathology</topic><topic>Chondrocytes - metabolism</topic><topic>Chondrocytes - pathology</topic><topic>Collagen</topic><topic>Collagen - biosynthesis</topic><topic>Collagen - genetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation</topic><topic>Histology</topic><topic>Humans</topic><topic>Hypertrophy - genetics</topic><topic>Hypertrophy - metabolism</topic><topic>Joint surgery</topic><topic>Knee Joint - physiopathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Osteoarthritis, Knee - genetics</topic><topic>Osteoarthritis, Knee - metabolism</topic><topic>Osteoarthritis, Knee - pathology</topic><topic>Principal components analysis</topic><topic>RNA, Messenger - genetics</topic><topic>SOX9 Transcription Factor - biosynthesis</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>Standard scores</topic><topic>Weight-Bearing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brew, C J</creatorcontrib><creatorcontrib>Clegg, P D</creatorcontrib><creatorcontrib>Boot-Handford, R P</creatorcontrib><creatorcontrib>Andrew, J G</creatorcontrib><creatorcontrib>Hardingham, T</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brew, C J</au><au>Clegg, P D</au><au>Boot-Handford, R P</au><au>Andrew, J G</au><au>Hardingham, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2010-01</date><risdate>2010</risdate><volume>69</volume><issue>1</issue><spage>234</spage><epage>240</epage><pages>234-240</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract><![CDATA[Objectives:To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.Methods:Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.Results:There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).Conclusions:The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.]]></abstract><cop>England</cop><pub>BMJ Publishing Group Ltd and European League Against Rheumatism</pub><pmid>19103633</pmid><doi>10.1136/ard.2008.097139</doi><tpages>7</tpages></addata></record> |
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| subjects | Age Aged Aged, 80 and over Aggrecans - biosynthesis Aggrecans - genetics Arthritis Cartilage, Articular - metabolism Cartilage, Articular - pathology Chondrocytes - metabolism Chondrocytes - pathology Collagen Collagen - biosynthesis Collagen - genetics Female Gene expression Gene Expression Profiling - methods Gene Expression Regulation Histology Humans Hypertrophy - genetics Hypertrophy - metabolism Joint surgery Knee Joint - physiopathology Male Middle Aged Osteoarthritis, Knee - genetics Osteoarthritis, Knee - metabolism Osteoarthritis, Knee - pathology Principal components analysis RNA, Messenger - genetics SOX9 Transcription Factor - biosynthesis SOX9 Transcription Factor - genetics Standard scores Weight-Bearing |
| title | Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy |
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