Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs
Objective Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been ide...
Gespeichert in:
| Veröffentlicht in: | Arthritis and rheumatism 2009-02, Vol.60 (2), p.460-469 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 469 |
|---|---|
| container_issue | 2 |
| container_start_page | 460 |
| container_title | Arthritis and rheumatism |
| container_volume | 60 |
| creator | Le Maitre, Christine Lyn Frain, Jennie Millward‐Sadler, Jane Fotheringham, Andrew P. Freemont, Anthony John Hoyland, Judith Alison |
| description | Objective
Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with α5β1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.
Methods
Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the α5β1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real‐time quantitative polymerase chain reaction.
Results
Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the α5β1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.
Conclusion
Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the α5β1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins. |
| doi_str_mv | 10.1002/art.24248 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66893761</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66893761</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3538-3aaa5e0fe4459fec61deb27904cd95c4c78d25204b669efe303ed0905edfcbbd3</originalsourceid><addsrcrecordid>eNp1kF1LwzAUhoMoOqcX_gHpjYIX3fLVrrkcwy8YCDKvS5qcbpU2rUmj7N-b2aJXXiUneXjfw4PQFcEzgjGdS9vPKKc8O0ITklARY8LIMZpgjHnMEkHO0Llz72GkLGGn6IwIkmGe4QlSy7oHCzqqTA9bW5moAbWTpu2tNE571VetCZ_RzjfSRMarGryLOl93rQsXBXXtIg22-gwhpW2bMGzBgJV9eNCVU-4CnZSydnA5nlP09nC_WT3F65fH59VyHauwVRYzKWUCuATOE1GCSomGgi4E5kqLRHG1yDRNKOZFmgoogWEGGgucgC5VUWg2RbdDbmfbDw-uz5tQHxaUBlrv8jTNBFukJIB3A6hs65yFMu9s1Ui7zwnOD0bzYDT_MRrY6zHUFw3oP3JUGICbEZBOyboM3lTlfjlKSEoEPZTOB-6rqmH_f2O-fN0M1d9p54-W</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66893761</pqid></control><display><type>article</type><title>Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Le Maitre, Christine Lyn ; Frain, Jennie ; Millward‐Sadler, Jane ; Fotheringham, Andrew P. ; Freemont, Anthony John ; Hoyland, Judith Alison</creator><creatorcontrib>Le Maitre, Christine Lyn ; Frain, Jennie ; Millward‐Sadler, Jane ; Fotheringham, Andrew P. ; Freemont, Anthony John ; Hoyland, Judith Alison</creatorcontrib><description>Objective
Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with α5β1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.
Methods
Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the α5β1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real‐time quantitative polymerase chain reaction.
Results
Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the α5β1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.
Conclusion
Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the α5β1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/art.24248</identifier><identifier>PMID: 19180480</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Aggrecans - genetics ; Aggrecans - metabolism ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Diseases of the osteoarticular system ; Female ; Gene Expression - drug effects ; Humans ; Immunohistochemistry ; Integrin alpha5beta1 - genetics ; Integrin alpha5beta1 - metabolism ; Integrins - genetics ; Integrins - metabolism ; Intervertebral Disc - drug effects ; Intervertebral Disc - metabolism ; Intervertebral Disc - pathology ; Intervertebral Disc Displacement - metabolism ; Intervertebral Disc Displacement - pathology ; Male ; Mechanotransduction, Cellular - drug effects ; Mechanotransduction, Cellular - physiology ; Medical sciences ; Middle Aged ; Oligopeptides - pharmacology ; Pressure ; RNA, Messenger - metabolism ; Weight-Bearing ; Young Adult</subject><ispartof>Arthritis and rheumatism, 2009-02, Vol.60 (2), p.460-469</ispartof><rights>Copyright © 2009 by the American College of Rheumatology</rights><rights>2009 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-3aaa5e0fe4459fec61deb27904cd95c4c78d25204b669efe303ed0905edfcbbd3</citedby><cites>FETCH-LOGICAL-c3538-3aaa5e0fe4459fec61deb27904cd95c4c78d25204b669efe303ed0905edfcbbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.24248$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.24248$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21161921$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19180480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Le Maitre, Christine Lyn</creatorcontrib><creatorcontrib>Frain, Jennie</creatorcontrib><creatorcontrib>Millward‐Sadler, Jane</creatorcontrib><creatorcontrib>Fotheringham, Andrew P.</creatorcontrib><creatorcontrib>Freemont, Anthony John</creatorcontrib><creatorcontrib>Hoyland, Judith Alison</creatorcontrib><title>Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with α5β1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.
Methods
Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the α5β1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real‐time quantitative polymerase chain reaction.
Results
Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the α5β1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.
Conclusion
Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the α5β1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.</description><subject>Adult</subject><subject>Aged</subject><subject>Aggrecans - genetics</subject><subject>Aggrecans - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Integrin alpha5beta1 - genetics</subject><subject>Integrin alpha5beta1 - metabolism</subject><subject>Integrins - genetics</subject><subject>Integrins - metabolism</subject><subject>Intervertebral Disc - drug effects</subject><subject>Intervertebral Disc - metabolism</subject><subject>Intervertebral Disc - pathology</subject><subject>Intervertebral Disc Displacement - metabolism</subject><subject>Intervertebral Disc Displacement - pathology</subject><subject>Male</subject><subject>Mechanotransduction, Cellular - drug effects</subject><subject>Mechanotransduction, Cellular - physiology</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oligopeptides - pharmacology</subject><subject>Pressure</subject><subject>RNA, Messenger - metabolism</subject><subject>Weight-Bearing</subject><subject>Young Adult</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF1LwzAUhoMoOqcX_gHpjYIX3fLVrrkcwy8YCDKvS5qcbpU2rUmj7N-b2aJXXiUneXjfw4PQFcEzgjGdS9vPKKc8O0ITklARY8LIMZpgjHnMEkHO0Llz72GkLGGn6IwIkmGe4QlSy7oHCzqqTA9bW5moAbWTpu2tNE571VetCZ_RzjfSRMarGryLOl93rQsXBXXtIg22-gwhpW2bMGzBgJV9eNCVU-4CnZSydnA5nlP09nC_WT3F65fH59VyHauwVRYzKWUCuATOE1GCSomGgi4E5kqLRHG1yDRNKOZFmgoogWEGGgucgC5VUWg2RbdDbmfbDw-uz5tQHxaUBlrv8jTNBFukJIB3A6hs65yFMu9s1Ui7zwnOD0bzYDT_MRrY6zHUFw3oP3JUGICbEZBOyboM3lTlfjlKSEoEPZTOB-6rqmH_f2O-fN0M1d9p54-W</recordid><startdate>200902</startdate><enddate>200902</enddate><creator>Le Maitre, Christine Lyn</creator><creator>Frain, Jennie</creator><creator>Millward‐Sadler, Jane</creator><creator>Fotheringham, Andrew P.</creator><creator>Freemont, Anthony John</creator><creator>Hoyland, Judith Alison</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>200902</creationdate><title>Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs</title><author>Le Maitre, Christine Lyn ; Frain, Jennie ; Millward‐Sadler, Jane ; Fotheringham, Andrew P. ; Freemont, Anthony John ; Hoyland, Judith Alison</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-3aaa5e0fe4459fec61deb27904cd95c4c78d25204b669efe303ed0905edfcbbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aggrecans - genetics</topic><topic>Aggrecans - metabolism</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>Gene Expression - drug effects</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Integrin alpha5beta1 - genetics</topic><topic>Integrin alpha5beta1 - metabolism</topic><topic>Integrins - genetics</topic><topic>Integrins - metabolism</topic><topic>Intervertebral Disc - drug effects</topic><topic>Intervertebral Disc - metabolism</topic><topic>Intervertebral Disc - pathology</topic><topic>Intervertebral Disc Displacement - metabolism</topic><topic>Intervertebral Disc Displacement - pathology</topic><topic>Male</topic><topic>Mechanotransduction, Cellular - drug effects</topic><topic>Mechanotransduction, Cellular - physiology</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oligopeptides - pharmacology</topic><topic>Pressure</topic><topic>RNA, Messenger - metabolism</topic><topic>Weight-Bearing</topic><topic>Young Adult</topic><toplevel>online_resources</toplevel><creatorcontrib>Le Maitre, Christine Lyn</creatorcontrib><creatorcontrib>Frain, Jennie</creatorcontrib><creatorcontrib>Millward‐Sadler, Jane</creatorcontrib><creatorcontrib>Fotheringham, Andrew P.</creatorcontrib><creatorcontrib>Freemont, Anthony John</creatorcontrib><creatorcontrib>Hoyland, Judith Alison</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Le Maitre, Christine Lyn</au><au>Frain, Jennie</au><au>Millward‐Sadler, Jane</au><au>Fotheringham, Andrew P.</au><au>Freemont, Anthony John</au><au>Hoyland, Judith Alison</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>2009-02</date><risdate>2009</risdate><volume>60</volume><issue>2</issue><spage>460</spage><epage>469</epage><pages>460-469</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><coden>ARHEAW</coden><abstract>Objective
Several studies have demonstrated biologic responses of intervertebral disc (IVD) cells to loading, although the mechanotransduction pathways have not been elucidated. In articular chondrocytes, which have a phenotype similar to that of IVD cells, a number of mechanoreceptors have been identified, with α5β1 integrin acting as a predominant mechanoreceptor. The purpose of this study was to investigate the role of integrin signaling in IVD cells during mechanical stimulation and to determine whether RGD integrins are involved.
Methods
Human nucleus pulposus (NP) cells derived from nondegenerated and degenerated discs were subjected to dynamic compressive loading in the presence of an RGD inhibitory peptide. Expression of the α5β1 heterodimer in IVD tissue was examined by immunohistochemistry and possible alternative mechanoreceptors by real‐time quantitative polymerase chain reaction.
Results
Aggrecan gene expression was decreased following loading of NP cells from nondegenerated and degenerated discs. This response was inhibited by treatment with an RGD peptide in cells from nondegenerated, but not degenerated, IVDs. Immunohistochemistry demonstrated that expression of the α5β1 heterodimer was unaltered in degenerated IVD tissue as compared with normal IVD tissue.
Conclusion
Our results indicate that the mechanotransduction pathways are altered in cells from degenerated IVDs. Mechanosensing in NP cells from nondegenerated discs occurs via RGD integrins, possibly via the α5β1 integrin, while cells from degenerated discs show a different signaling pathway that does not appear to involve RGD integrins.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19180480</pmid><doi>10.1002/art.24248</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0004-3591 |
| ispartof | Arthritis and rheumatism, 2009-02, Vol.60 (2), p.460-469 |
| issn | 0004-3591 1529-0131 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_66893761 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Adult Aged Aggrecans - genetics Aggrecans - metabolism Antineoplastic Agents - pharmacology Biological and medical sciences Diseases of the osteoarticular system Female Gene Expression - drug effects Humans Immunohistochemistry Integrin alpha5beta1 - genetics Integrin alpha5beta1 - metabolism Integrins - genetics Integrins - metabolism Intervertebral Disc - drug effects Intervertebral Disc - metabolism Intervertebral Disc - pathology Intervertebral Disc Displacement - metabolism Intervertebral Disc Displacement - pathology Male Mechanotransduction, Cellular - drug effects Mechanotransduction, Cellular - physiology Medical sciences Middle Aged Oligopeptides - pharmacology Pressure RNA, Messenger - metabolism Weight-Bearing Young Adult |
| title | Altered integrin mechanotransduction in human nucleus pulposus cells derived from degenerated discs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T16%3A08%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Altered%20integrin%20mechanotransduction%20in%20human%20nucleus%20pulposus%20cells%20derived%20from%20degenerated%20discs&rft.jtitle=Arthritis%20and%20rheumatism&rft.au=Le%20Maitre,%20Christine%20Lyn&rft.date=2009-02&rft.volume=60&rft.issue=2&rft.spage=460&rft.epage=469&rft.pages=460-469&rft.issn=0004-3591&rft.eissn=1529-0131&rft.coden=ARHEAW&rft_id=info:doi/10.1002/art.24248&rft_dat=%3Cproquest_cross%3E66893761%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66893761&rft_id=info:pmid/19180480&rfr_iscdi=true |