Asporin expression is highly regulated in human chondrocytes
A significant association between a polymorphism in the D repeat of the gene encoding asporin and osteoarthritis, the most frequent of articular diseases, has been recently reported. The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (...
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| Veröffentlicht in: | Molecular medicine (Cambridge, Mass.) Mass.), 2011-07, Vol.17 (7-8), p.816-823 |
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| creator | Duval, Elise Bigot, Nicolas Hervieu, Magalie Kou, Ikuyo Leclercq, Sylvain Galéra, Philippe Boumediene, Karim Baugé, Catherine |
| description | A significant association between a polymorphism in the D repeat of the gene encoding asporin and osteoarthritis, the most frequent of articular diseases, has been recently reported. The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (SLRP) in human articular chondrocytes. First, we studied the modulation of asporin (ASPN) expression by cytokines by Western blot and reverse transcription-polymerase chain reaction. Interleukin-1β and tumor necrosis factor-α downregulated ASPN, whereas transforming growth factor-β1 (when incubated in a serum-free medium) upregulated it. Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced by a successive passages of cells was accompanied by a decreased asporin expression, whereas their redifferentiation by three-dimensional culture restored its expression. Finally, we found an important role of the transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic expression increased ASPN mRNA level and promoter activity. In addition, using gene reporter assay and electrophoretic mobility shift assay, we showed that Sp1 mediated its effect through a region located between -473 and -140 bp upstream of the transcription start site in ASPN gene. In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in human articular chondrocytes. Our data indicate that the expression of this gene is finely regulated in cartilage and suggest a major role of Sp1. |
| doi_str_mv | 10.2119/molmed.2011.00052 |
| format | Article |
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The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (SLRP) in human articular chondrocytes. First, we studied the modulation of asporin (ASPN) expression by cytokines by Western blot and reverse transcription-polymerase chain reaction. Interleukin-1β and tumor necrosis factor-α downregulated ASPN, whereas transforming growth factor-β1 (when incubated in a serum-free medium) upregulated it. Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced by a successive passages of cells was accompanied by a decreased asporin expression, whereas their redifferentiation by three-dimensional culture restored its expression. Finally, we found an important role of the transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic expression increased ASPN mRNA level and promoter activity. In addition, using gene reporter assay and electrophoretic mobility shift assay, we showed that Sp1 mediated its effect through a region located between -473 and -140 bp upstream of the transcription start site in ASPN gene. In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in human articular chondrocytes. Our data indicate that the expression of this gene is finely regulated in cartilage and suggest a major role of Sp1.</description><identifier>ISSN: 1076-1551</identifier><identifier>EISSN: 1528-3658</identifier><identifier>DOI: 10.2119/molmed.2011.00052</identifier><identifier>PMID: 21528154</identifier><language>eng</language><publisher>England: Feinstein Institute for Medical Research</publisher><subject>Aged ; Aged, 80 and over ; Binding Sites - genetics ; Biochemistry, Molecular Biology ; Blotting, Western ; Cartilage ; Cartilage, Articular - cytology ; Cell Dedifferentiation - genetics ; Cell Differentiation - genetics ; Cells, Cultured ; Cellular Biology ; Chondrocytes ; Chondrocytes - cytology ; Chondrocytes - drug effects ; Chondrocytes - metabolism ; Cytokines ; Down-Regulation - drug effects ; Electrophoretic Mobility Shift Assay ; Extracellular Matrix Proteins - genetics ; Extracellular Matrix Proteins - metabolism ; Gene Expression - drug effects ; Gene Expression - genetics ; Human health and pathology ; Humans ; Interleukin-1beta ; Interleukin-1beta - pharmacology ; Life Sciences ; Middle Aged ; Osteoarthritis ; Polymerase Chain Reaction ; Primary Cell Culture ; Promoter Regions, Genetic - genetics ; Protein Binding ; Proteoglycans ; Reverse Transcriptase Polymerase Chain Reaction ; Reverse Transcription ; Rhumatology and musculoskeletal system ; RNA, Messenger ; Sp1 Transcription Factor ; Sp1 Transcription Factor - genetics ; Sp1 Transcription Factor - metabolism ; Transfection ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta1 - pharmacology ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factor-alpha - pharmacology</subject><ispartof>Molecular medicine (Cambridge, Mass.), 2011-07, Vol.17 (7-8), p.816-823</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright 2011, The Feinstein Institute for Medical Research 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-dc8b194df6cb63f6123788a71c57458b13bad51a6797c04c13f59cdf8dcc23df3</citedby><cites>FETCH-LOGICAL-c498t-dc8b194df6cb63f6123788a71c57458b13bad51a6797c04c13f59cdf8dcc23df3</cites><orcidid>0000-0002-7797-2284 ; 0000-0001-5642-998X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146605/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146605/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21528154$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01149586$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Duval, Elise</creatorcontrib><creatorcontrib>Bigot, Nicolas</creatorcontrib><creatorcontrib>Hervieu, Magalie</creatorcontrib><creatorcontrib>Kou, Ikuyo</creatorcontrib><creatorcontrib>Leclercq, Sylvain</creatorcontrib><creatorcontrib>Galéra, Philippe</creatorcontrib><creatorcontrib>Boumediene, Karim</creatorcontrib><creatorcontrib>Baugé, Catherine</creatorcontrib><title>Asporin expression is highly regulated in human chondrocytes</title><title>Molecular medicine (Cambridge, Mass.)</title><addtitle>Mol Med</addtitle><description>A significant association between a polymorphism in the D repeat of the gene encoding asporin and osteoarthritis, the most frequent of articular diseases, has been recently reported. The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (SLRP) in human articular chondrocytes. First, we studied the modulation of asporin (ASPN) expression by cytokines by Western blot and reverse transcription-polymerase chain reaction. Interleukin-1β and tumor necrosis factor-α downregulated ASPN, whereas transforming growth factor-β1 (when incubated in a serum-free medium) upregulated it. Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced by a successive passages of cells was accompanied by a decreased asporin expression, whereas their redifferentiation by three-dimensional culture restored its expression. Finally, we found an important role of the transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic expression increased ASPN mRNA level and promoter activity. In addition, using gene reporter assay and electrophoretic mobility shift assay, we showed that Sp1 mediated its effect through a region located between -473 and -140 bp upstream of the transcription start site in ASPN gene. In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in human articular chondrocytes. Our data indicate that the expression of this gene is finely regulated in cartilage and suggest a major role of Sp1.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Binding Sites - genetics</subject><subject>Biochemistry, Molecular Biology</subject><subject>Blotting, Western</subject><subject>Cartilage</subject><subject>Cartilage, Articular - cytology</subject><subject>Cell Dedifferentiation - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>Cells, Cultured</subject><subject>Cellular Biology</subject><subject>Chondrocytes</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - drug effects</subject><subject>Chondrocytes - metabolism</subject><subject>Cytokines</subject><subject>Down-Regulation - drug effects</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Extracellular Matrix Proteins - genetics</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression - genetics</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Interleukin-1beta</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Life Sciences</subject><subject>Middle Aged</subject><subject>Osteoarthritis</subject><subject>Polymerase Chain Reaction</subject><subject>Primary Cell Culture</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Binding</subject><subject>Proteoglycans</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Reverse Transcription</subject><subject>Rhumatology and musculoskeletal system</subject><subject>RNA, Messenger</subject><subject>Sp1 Transcription Factor</subject><subject>Sp1 Transcription Factor - genetics</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Transfection</subject><subject>Transforming Growth Factor beta1</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><issn>1076-1551</issn><issn>1528-3658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1LxDAQhoMo7rr6A7xIrx66ZpImTUGEZfELFrzoOaRJuq30Y0m6i_vvTa0u6mmGmfd9mXkQugQ8JwDZTdPVjTVzggHmGGNGjtAUGBEx5Uwchx6nPAbGYILOvH_HmABL2CmakEEV-im6XfhN56o2sh8bZ72vujaqfFRW67LeR86ut7XqrYmCotw2qo102bXGdXrfW3-OTgpVe3vxXWfo7eH-dfkUr14en5eLVayTTPSx0SKHLDEF1zmnBQdCUyFUCpqlCQs7mivDQPE0SzVONNCCZdoUwmhNqCnoDN2NuZttHh7Wtu2dquXGVY1ye9mpSv7dtFUp191OUkg4xywEXI8B5T_b02Ilh1kgmGRM8B0ELYxa7TrvnS0OBsBywC5H7HLALr-wB8_V7wMPjh_O9BNjO4C6</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Duval, Elise</creator><creator>Bigot, Nicolas</creator><creator>Hervieu, Magalie</creator><creator>Kou, Ikuyo</creator><creator>Leclercq, Sylvain</creator><creator>Galéra, Philippe</creator><creator>Boumediene, Karim</creator><creator>Baugé, Catherine</creator><general>Feinstein Institute for Medical Research</general><general>ScholarOne</general><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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7797-2284</orcidid><orcidid>https://orcid.org/0000-0001-5642-998X</orcidid></search><sort><creationdate>20110701</creationdate><title>Asporin expression is highly regulated in human chondrocytes</title><author>Duval, Elise ; Bigot, Nicolas ; Hervieu, Magalie ; Kou, Ikuyo ; Leclercq, Sylvain ; Galéra, Philippe ; Boumediene, Karim ; Baugé, Catherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-dc8b194df6cb63f6123788a71c57458b13bad51a6797c04c13f59cdf8dcc23df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Binding Sites - genetics</topic><topic>Biochemistry, Molecular Biology</topic><topic>Blotting, Western</topic><topic>Cartilage</topic><topic>Cartilage, Articular - cytology</topic><topic>Cell Dedifferentiation - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>Cells, Cultured</topic><topic>Cellular Biology</topic><topic>Chondrocytes</topic><topic>Chondrocytes - cytology</topic><topic>Chondrocytes - drug effects</topic><topic>Chondrocytes - metabolism</topic><topic>Cytokines</topic><topic>Down-Regulation - drug effects</topic><topic>Electrophoretic Mobility Shift Assay</topic><topic>Extracellular Matrix Proteins - genetics</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression - genetics</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Interleukin-1beta</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Life Sciences</topic><topic>Middle Aged</topic><topic>Osteoarthritis</topic><topic>Polymerase Chain Reaction</topic><topic>Primary Cell Culture</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Binding</topic><topic>Proteoglycans</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Reverse Transcription</topic><topic>Rhumatology and musculoskeletal system</topic><topic>RNA, Messenger</topic><topic>Sp1 Transcription Factor</topic><topic>Sp1 Transcription Factor - genetics</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Transfection</topic><topic>Transforming Growth Factor beta1</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duval, Elise</creatorcontrib><creatorcontrib>Bigot, Nicolas</creatorcontrib><creatorcontrib>Hervieu, Magalie</creatorcontrib><creatorcontrib>Kou, Ikuyo</creatorcontrib><creatorcontrib>Leclercq, Sylvain</creatorcontrib><creatorcontrib>Galéra, Philippe</creatorcontrib><creatorcontrib>Boumediene, Karim</creatorcontrib><creatorcontrib>Baugé, Catherine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duval, Elise</au><au>Bigot, Nicolas</au><au>Hervieu, Magalie</au><au>Kou, Ikuyo</au><au>Leclercq, Sylvain</au><au>Galéra, Philippe</au><au>Boumediene, Karim</au><au>Baugé, Catherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Asporin expression is highly regulated in human chondrocytes</atitle><jtitle>Molecular medicine (Cambridge, Mass.)</jtitle><addtitle>Mol Med</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>17</volume><issue>7-8</issue><spage>816</spage><epage>823</epage><pages>816-823</pages><issn>1076-1551</issn><eissn>1528-3658</eissn><abstract>A significant association between a polymorphism in the D repeat of the gene encoding asporin and osteoarthritis, the most frequent of articular diseases, has been recently reported. The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (SLRP) in human articular chondrocytes. First, we studied the modulation of asporin (ASPN) expression by cytokines by Western blot and reverse transcription-polymerase chain reaction. Interleukin-1β and tumor necrosis factor-α downregulated ASPN, whereas transforming growth factor-β1 (when incubated in a serum-free medium) upregulated it. Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced by a successive passages of cells was accompanied by a decreased asporin expression, whereas their redifferentiation by three-dimensional culture restored its expression. Finally, we found an important role of the transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic expression increased ASPN mRNA level and promoter activity. In addition, using gene reporter assay and electrophoretic mobility shift assay, we showed that Sp1 mediated its effect through a region located between -473 and -140 bp upstream of the transcription start site in ASPN gene. In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in human articular chondrocytes. Our data indicate that the expression of this gene is finely regulated in cartilage and suggest a major role of Sp1.</abstract><cop>England</cop><pub>Feinstein Institute for Medical Research</pub><pmid>21528154</pmid><doi>10.2119/molmed.2011.00052</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7797-2284</orcidid><orcidid>https://orcid.org/0000-0001-5642-998X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Binding Sites - genetics Biochemistry, Molecular Biology Blotting, Western Cartilage Cartilage, Articular - cytology Cell Dedifferentiation - genetics Cell Differentiation - genetics Cells, Cultured Cellular Biology Chondrocytes Chondrocytes - cytology Chondrocytes - drug effects Chondrocytes - metabolism Cytokines Down-Regulation - drug effects Electrophoretic Mobility Shift Assay Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Gene Expression - drug effects Gene Expression - genetics Human health and pathology Humans Interleukin-1beta Interleukin-1beta - pharmacology Life Sciences Middle Aged Osteoarthritis Polymerase Chain Reaction Primary Cell Culture Promoter Regions, Genetic - genetics Protein Binding Proteoglycans Reverse Transcriptase Polymerase Chain Reaction Reverse Transcription Rhumatology and musculoskeletal system RNA, Messenger Sp1 Transcription Factor Sp1 Transcription Factor - genetics Sp1 Transcription Factor - metabolism Transfection Transforming Growth Factor beta1 Transforming Growth Factor beta1 - pharmacology Tumor Necrosis Factor-alpha Tumor Necrosis Factor-alpha - pharmacology |
| title | Asporin expression is highly regulated in human chondrocytes |
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