YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity
Matrix elasticity exerts considerable influence on the phenotype of terminally differentiated chondrocytes via physical cues. The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator that may be involved in the nuclear transduction of physical cues controlling cell...
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Veröffentlicht in: | Journal of molecular histology 2013-10, Vol.44 (5), p.587-595 |
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description | Matrix elasticity exerts considerable influence on the phenotype of terminally differentiated chondrocytes via physical cues. The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator that may be involved in the nuclear transduction of physical cues controlling cellular behavior and function. However, whether substrate elasticity in the regulation of the chondrocyte phenotype is associated with YAP remains unclear. In this work, we developed micropatterned substrates with varying stiffnesses to investigate the function of YAP and its related Hippo pathway kinases in the regulation of chondrocyte phenotype on soft and stiff substrates. We found that the phenotypic variation of chondrocytes in response to substrate stiffness is concomitant with the changes in YAP localization. The downregulation of YAP expression helps to maintain the chondrogenic phenotype while inhibiting chondrocyte proliferation. Furthermore, the change in the chondrocyte phenotype response to LATS1 kinase inactivation in the Hippo pathway varies significantly between soft and stiff substrates. We also found that LATS1 kinase inactivation promotes chondrocyte dedifferentiation only on stiff substrate. Collectively, these findings reveal that YAP may be involved in the changes that occur in chondrocytes cultured on substrates with different stiffnesses and that these changes do not entirely depend on the Hippo pathway kinase LATS1. Importantly, our findings indicate that YAP inactivation is conducive to the maintenance of the chondrogenic phenotype, thereby providing new insight into articular cartilage repair and regeneration mechanisms. |
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The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator that may be involved in the nuclear transduction of physical cues controlling cellular behavior and function. However, whether substrate elasticity in the regulation of the chondrocyte phenotype is associated with YAP remains unclear. In this work, we developed micropatterned substrates with varying stiffnesses to investigate the function of YAP and its related Hippo pathway kinases in the regulation of chondrocyte phenotype on soft and stiff substrates. We found that the phenotypic variation of chondrocytes in response to substrate stiffness is concomitant with the changes in YAP localization. The downregulation of YAP expression helps to maintain the chondrogenic phenotype while inhibiting chondrocyte proliferation. Furthermore, the change in the chondrocyte phenotype response to LATS1 kinase inactivation in the Hippo pathway varies significantly between soft and stiff substrates. We also found that LATS1 kinase inactivation promotes chondrocyte dedifferentiation only on stiff substrate. Collectively, these findings reveal that YAP may be involved in the changes that occur in chondrocytes cultured on substrates with different stiffnesses and that these changes do not entirely depend on the Hippo pathway kinase LATS1. Importantly, our findings indicate that YAP inactivation is conducive to the maintenance of the chondrogenic phenotype, thereby providing new insight into articular cartilage repair and regeneration mechanisms.</description><identifier>ISSN: 1567-2379</identifier><identifier>EISSN: 1567-2387</identifier><identifier>DOI: 10.1007/s10735-013-9502-y</identifier><identifier>PMID: 23543231</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Acrylic Resins - chemistry ; Animals ; Apoptosis Regulatory Proteins - antagonists & inhibitors ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cartilage, Articular - cytology ; Cartilage, Articular - metabolism ; Cell Biology ; Cell Proliferation ; Chondrocytes - cytology ; Chondrocytes - metabolism ; Developmental Biology ; Dimethylpolysiloxanes - chemistry ; Elasticity ; Gene Expression Regulation ; Hardness ; Life Sciences ; Male ; Original Paper ; Phenotype ; Primary Cell Culture ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Rats ; Rats, Sprague-Dawley ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; Signal Transduction ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism</subject><ispartof>Journal of molecular histology, 2013-10, Vol.44 (5), p.587-595</ispartof><rights>Springer Science+Business Media Dordrecht 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-451c530bc079a4f0d1e3e173ef4b75283a1170c6736c24e1c44bb8188930fe823</citedby><cites>FETCH-LOGICAL-c508t-451c530bc079a4f0d1e3e173ef4b75283a1170c6736c24e1c44bb8188930fe823</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10735-013-9502-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10735-013-9502-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23543231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhong, Weiliang</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Li, Linan</creatorcontrib><creatorcontrib>Zhang, Weiguo</creatorcontrib><creatorcontrib>Wang, Shouyu</creatorcontrib><creatorcontrib>Zheng, Xifu</creatorcontrib><title>YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity</title><title>Journal of molecular histology</title><addtitle>J Mol Hist</addtitle><addtitle>J Mol Histol</addtitle><description>Matrix elasticity exerts considerable influence on the phenotype of terminally differentiated chondrocytes via physical cues. The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator that may be involved in the nuclear transduction of physical cues controlling cellular behavior and function. However, whether substrate elasticity in the regulation of the chondrocyte phenotype is associated with YAP remains unclear. In this work, we developed micropatterned substrates with varying stiffnesses to investigate the function of YAP and its related Hippo pathway kinases in the regulation of chondrocyte phenotype on soft and stiff substrates. We found that the phenotypic variation of chondrocytes in response to substrate stiffness is concomitant with the changes in YAP localization. The downregulation of YAP expression helps to maintain the chondrogenic phenotype while inhibiting chondrocyte proliferation. Furthermore, the change in the chondrocyte phenotype response to LATS1 kinase inactivation in the Hippo pathway varies significantly between soft and stiff substrates. We also found that LATS1 kinase inactivation promotes chondrocyte dedifferentiation only on stiff substrate. Collectively, these findings reveal that YAP may be involved in the changes that occur in chondrocytes cultured on substrates with different stiffnesses and that these changes do not entirely depend on the Hippo pathway kinase LATS1. Importantly, our findings indicate that YAP inactivation is conducive to the maintenance of the chondrogenic phenotype, thereby providing new insight into articular cartilage repair and regeneration mechanisms.</description><subject>Acrylic Resins - chemistry</subject><subject>Animals</subject><subject>Apoptosis Regulatory Proteins - antagonists & inhibitors</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cartilage, Articular - cytology</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cell Biology</subject><subject>Cell Proliferation</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - metabolism</subject><subject>Developmental Biology</subject><subject>Dimethylpolysiloxanes - chemistry</subject><subject>Elasticity</subject><subject>Gene Expression Regulation</subject><subject>Hardness</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Original Paper</subject><subject>Phenotype</subject><subject>Primary Cell Culture</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Signal Transduction</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - metabolism</subject><issn>1567-2379</issn><issn>1567-2387</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNp1kE2LFDEQhoMo7of-AC8S8OKlNZVKT7qPy7LqwoIeVPAU0pnqmSw9SZukwf73Zph1EcFTFdRTbxUPY69AvAMh9PsMQmPbCMCmb4Vs1ifsHNqNbiR2-uljr_szdpHzvRCy26j-OTuT2CqUCOfs-4-rL82Btt4W2vJEu2WyxcfA48jLnrjbx7BNcUfBOz7vKcSyzsR9qGyeY8jES-QHW5L_xWmyuXjny_qCPRvtlOnlQ71k3z7cfL3-1Nx9_nh7fXXXuFZ0pVEtuBbF4ITurRrFFggJNNKoBt3KDi2AFm6jceOkInBKDUMHXdejGKmTeMnennLnFH8ulIs5-OxommyguGQDSiH2EnRf0Tf_oPdxSaF-VynUGpUUx0A4US7FnBONZk7-YNNqQJijdHOSbqp0c5Ru1rrz-iF5GarKx40_lisgT0Cuo7Cj9Nfp_6b-BuZqjD0</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Zhong, Weiliang</creator><creator>Li, Ying</creator><creator>Li, Linan</creator><creator>Zhang, Weiguo</creator><creator>Wang, Shouyu</creator><creator>Zheng, Xifu</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20131001</creationdate><title>YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity</title><author>Zhong, Weiliang ; Li, Ying ; Li, Linan ; Zhang, Weiguo ; Wang, Shouyu ; Zheng, Xifu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-451c530bc079a4f0d1e3e173ef4b75283a1170c6736c24e1c44bb8188930fe823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acrylic Resins - 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Academic</collection><jtitle>Journal of molecular histology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Weiliang</au><au>Li, Ying</au><au>Li, Linan</au><au>Zhang, Weiguo</au><au>Wang, Shouyu</au><au>Zheng, Xifu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity</atitle><jtitle>Journal of molecular histology</jtitle><stitle>J Mol Hist</stitle><addtitle>J Mol Histol</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>44</volume><issue>5</issue><spage>587</spage><epage>595</epage><pages>587-595</pages><issn>1567-2379</issn><eissn>1567-2387</eissn><abstract>Matrix elasticity exerts considerable influence on the phenotype of terminally differentiated chondrocytes via physical cues. The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator that may be involved in the nuclear transduction of physical cues controlling cellular behavior and function. However, whether substrate elasticity in the regulation of the chondrocyte phenotype is associated with YAP remains unclear. In this work, we developed micropatterned substrates with varying stiffnesses to investigate the function of YAP and its related Hippo pathway kinases in the regulation of chondrocyte phenotype on soft and stiff substrates. We found that the phenotypic variation of chondrocytes in response to substrate stiffness is concomitant with the changes in YAP localization. The downregulation of YAP expression helps to maintain the chondrogenic phenotype while inhibiting chondrocyte proliferation. Furthermore, the change in the chondrocyte phenotype response to LATS1 kinase inactivation in the Hippo pathway varies significantly between soft and stiff substrates. We also found that LATS1 kinase inactivation promotes chondrocyte dedifferentiation only on stiff substrate. Collectively, these findings reveal that YAP may be involved in the changes that occur in chondrocytes cultured on substrates with different stiffnesses and that these changes do not entirely depend on the Hippo pathway kinase LATS1. Importantly, our findings indicate that YAP inactivation is conducive to the maintenance of the chondrogenic phenotype, thereby providing new insight into articular cartilage repair and regeneration mechanisms.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>23543231</pmid><doi>10.1007/s10735-013-9502-y</doi><tpages>9</tpages></addata></record> |
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subjects | Acrylic Resins - chemistry Animals Apoptosis Regulatory Proteins - antagonists & inhibitors Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Biomedical and Life Sciences Biomedicine Cartilage, Articular - cytology Cartilage, Articular - metabolism Cell Biology Cell Proliferation Chondrocytes - cytology Chondrocytes - metabolism Developmental Biology Dimethylpolysiloxanes - chemistry Elasticity Gene Expression Regulation Hardness Life Sciences Male Original Paper Phenotype Primary Cell Culture Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism Rats Rats, Sprague-Dawley RNA, Small Interfering - genetics RNA, Small Interfering - metabolism Signal Transduction SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism |
title | YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity |
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