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The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β
Abstract Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell...
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| Published in: | Biomaterials 2011-06, Vol.32 (16), p.3921-3930 |
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| creator | Park, Jennifer S Chu, Julia S Tsou, Anchi D Diop, Rokhaya Tang, Zhenyu Wang, Aijun Li, Song |
| description | Abstract Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration. |
| doi_str_mv | 10.1016/j.biomaterials.2011.02.019 |
| format | article |
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Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2011.02.019</identifier><identifier>PMID: 21397942</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Acrylic Resins - chemistry ; Advanced Basic Science ; Cell Adhesion ; Cell Differentiation - drug effects ; Cell Proliferation ; Cells, Cultured ; Chondrocyte ; Collagen Type II - metabolism ; Cytoskeleton - metabolism ; Dentistry ; Extracellular matrix ; Humans ; Immunoblotting ; Lipoprotein Lipase - metabolism ; Matrix rigidity ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - metabolism ; Polymerase Chain Reaction ; rho GTP-Binding Proteins - metabolism ; Smad2 Protein - metabolism ; Smad3 Protein - metabolism ; Smooth muscle cell ; Transforming Growth Factor beta - pharmacology</subject><ispartof>Biomaterials, 2011-06, Vol.32 (16), p.3921-3930</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><rights>2011 Elsevier Ltd. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-5510c63b1c249576e41ea42b26fef2e715b3e1d629c058f7dcd2c046c8c497ae3</citedby><cites>FETCH-LOGICAL-c573t-5510c63b1c249576e41ea42b26fef2e715b3e1d629c058f7dcd2c046c8c497ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21397942$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Jennifer S</creatorcontrib><creatorcontrib>Chu, Julia S</creatorcontrib><creatorcontrib>Tsou, Anchi D</creatorcontrib><creatorcontrib>Diop, Rokhaya</creatorcontrib><creatorcontrib>Tang, Zhenyu</creatorcontrib><creatorcontrib>Wang, Aijun</creatorcontrib><creatorcontrib>Li, Song</creatorcontrib><title>The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration.</description><subject>Acrylic Resins - chemistry</subject><subject>Advanced Basic Science</subject><subject>Cell Adhesion</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Chondrocyte</subject><subject>Collagen Type II - metabolism</subject><subject>Cytoskeleton - metabolism</subject><subject>Dentistry</subject><subject>Extracellular matrix</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Lipoprotein Lipase - metabolism</subject><subject>Matrix rigidity</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>rho GTP-Binding Proteins - metabolism</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 Protein - metabolism</subject><subject>Smooth muscle cell</subject><subject>Transforming Growth Factor beta - pharmacology</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqNksFu1DAQhi0EokvhFZDFhVOCx0mcmEMlVGhBqsSB5Ww5zpj1ktiLna3Y1-JB-kx1tKUqXOBk2f7_3zP-hpBXwEpgIN5sy96FSc8YnR5TyRlAyXjJQD4iK-jarmgkax6TFYOaF1IAPyHPUtqyvGc1f0pOOFSylTVfEVxvkKK1aGYaLM2p0f2kaXbWekyJBk_nrBjyHiP62enZ5bNFigm92RwmPWY9TtTgOCbqPI2YdsEnpHOg68uL4ubXc_LE5lLxxd16Sr5efFiffyyuPl9-On93VZimreaiaYAZUfVgeC2bVmANqGvec2HRcmyh6SuEQXBpWNPZdjADN6wWpjO1bDVWp-TsmLvb9xMOJhcc9ah20U06HlTQTv15491GfQvXqmJtJWWTA17fBcTwY49pVpNLS2PaY9gn1QnZVUIw-LdyYSBrIbLy7VFpYkgpor2vB5hagKqteghULUAV4yoDzeaXDzu6t_4mmAXvjwLM_3rtMKpkXAaDg4sZqhqC-793zv6KMaPzzujxOx4wbcM--sUDKmWD-rKM1jJZAHmqWuDVLXBQ0Bs</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Park, Jennifer S</creator><creator>Chu, Julia S</creator><creator>Tsou, Anchi D</creator><creator>Diop, Rokhaya</creator><creator>Tang, Zhenyu</creator><creator>Wang, Aijun</creator><creator>Li, Song</creator><general>Elsevier Ltd</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20110601</creationdate><title>The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β</title><author>Park, Jennifer S ; Chu, Julia S ; Tsou, Anchi D ; Diop, Rokhaya ; Tang, Zhenyu ; Wang, Aijun ; Li, Song</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-5510c63b1c249576e41ea42b26fef2e715b3e1d629c058f7dcd2c046c8c497ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acrylic Resins - chemistry</topic><topic>Advanced Basic Science</topic><topic>Cell Adhesion</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Chondrocyte</topic><topic>Collagen Type II - metabolism</topic><topic>Cytoskeleton - metabolism</topic><topic>Dentistry</topic><topic>Extracellular matrix</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Lipoprotein Lipase - metabolism</topic><topic>Matrix rigidity</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>rho GTP-Binding Proteins - metabolism</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 Protein - metabolism</topic><topic>Smooth muscle cell</topic><topic>Transforming Growth Factor beta - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Jennifer S</creatorcontrib><creatorcontrib>Chu, Julia S</creatorcontrib><creatorcontrib>Tsou, Anchi D</creatorcontrib><creatorcontrib>Diop, Rokhaya</creatorcontrib><creatorcontrib>Tang, Zhenyu</creatorcontrib><creatorcontrib>Wang, Aijun</creatorcontrib><creatorcontrib>Li, Song</creatorcontrib><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Jennifer S</au><au>Chu, Julia S</au><au>Tsou, Anchi D</au><au>Diop, Rokhaya</au><au>Tang, Zhenyu</au><au>Wang, Aijun</au><au>Li, Song</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>32</volume><issue>16</issue><spage>3921</spage><epage>3930</epage><pages>3921-3930</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>21397942</pmid><doi>10.1016/j.biomaterials.2011.02.019</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biomaterials, 2011-06, Vol.32 (16), p.3921-3930 |
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| source | ScienceDirect Freedom Collection |
| subjects | Acrylic Resins - chemistry Advanced Basic Science Cell Adhesion Cell Differentiation - drug effects Cell Proliferation Cells, Cultured Chondrocyte Collagen Type II - metabolism Cytoskeleton - metabolism Dentistry Extracellular matrix Humans Immunoblotting Lipoprotein Lipase - metabolism Matrix rigidity Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - metabolism Polymerase Chain Reaction rho GTP-Binding Proteins - metabolism Smad2 Protein - metabolism Smad3 Protein - metabolism Smooth muscle cell Transforming Growth Factor beta - pharmacology |
| title | The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β |
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