Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin
A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-β1), the most common growth factor used in chondrogenic induction me...
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| description | A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-β1), the most common growth factor used in chondrogenic induction medium. Herein, we directly compared the
in vitro
chondrogenic potency of TGF-β1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7–14 days in medium supplemented with TGF-β1, KGN, or both TGF-β1 + KGN. Following 14 days of induction, micropellets exposed to TGF-β1 alone or TGF-β1 + KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-β1 + KGN was used, GAG quantities were similar or slightly greater than the TGF-β1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-β1 + KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-β1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering. |
| doi_str_mv | 10.1038/s41598-020-65283-8 |
| format | Article |
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in vitro
chondrogenic potency of TGF-β1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7–14 days in medium supplemented with TGF-β1, KGN, or both TGF-β1 + KGN. Following 14 days of induction, micropellets exposed to TGF-β1 alone or TGF-β1 + KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-β1 + KGN was used, GAG quantities were similar or slightly greater than the TGF-β1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-β1 + KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-β1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-65283-8</identifier><identifier>PMID: 32433527</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/532/1360 ; 631/532/2074 ; 692/308/2171 ; Anilides - pharmacology ; Bone growth ; Bone marrow ; Cartilage ; Cartilage - growth & development ; Cell culture ; Cell Differentiation - drug effects ; Cells, Cultured ; Chondrogenesis ; Chondrogenesis - drug effects ; Culture Media - pharmacology ; Growth factors ; Humanities and Social Sciences ; Humans ; Hypertrophy ; Mesenchymal Stem Cells - drug effects ; Mesenchymal Stem Cells - physiology ; Mesenchyme ; multidisciplinary ; Phthalic Acids - pharmacology ; Physical growth ; Primary Cell Culture - methods ; Recombinant Proteins - pharmacology ; Science ; Science (multidisciplinary) ; Tissue engineering ; Tissue Engineering - methods ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1</subject><ispartof>Scientific reports, 2020-05, Vol.10 (1), p.8340-8340, Article 8340</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-ac0af517a785e898fff2804bf3ea9a13113c87bd667b629195aa131834549edd3</citedby><cites>FETCH-LOGICAL-c511t-ac0af517a785e898fff2804bf3ea9a13113c87bd667b629195aa131834549edd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239921/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239921/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51555,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32433527$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Music, E.</creatorcontrib><creatorcontrib>Klein, T. J.</creatorcontrib><creatorcontrib>Lott, W. B.</creatorcontrib><creatorcontrib>Doran, M. R.</creatorcontrib><title>Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-β1), the most common growth factor used in chondrogenic induction medium. Herein, we directly compared the
in vitro
chondrogenic potency of TGF-β1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7–14 days in medium supplemented with TGF-β1, KGN, or both TGF-β1 + KGN. Following 14 days of induction, micropellets exposed to TGF-β1 alone or TGF-β1 + KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-β1 + KGN was used, GAG quantities were similar or slightly greater than the TGF-β1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-β1 + KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-β1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering.</description><subject>631/532/1360</subject><subject>631/532/2074</subject><subject>692/308/2171</subject><subject>Anilides - pharmacology</subject><subject>Bone growth</subject><subject>Bone marrow</subject><subject>Cartilage</subject><subject>Cartilage - growth & development</subject><subject>Cell culture</subject><subject>Cell Differentiation - drug effects</subject><subject>Cells, Cultured</subject><subject>Chondrogenesis</subject><subject>Chondrogenesis - drug effects</subject><subject>Culture Media - pharmacology</subject><subject>Growth factors</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hypertrophy</subject><subject>Mesenchymal Stem Cells - drug effects</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Mesenchyme</subject><subject>multidisciplinary</subject><subject>Phthalic Acids - pharmacology</subject><subject>Physical growth</subject><subject>Primary Cell Culture - methods</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Transforming growth factor-b1</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp9kctu1TAURS0EolXpDzBAlpgwCfUjvrEnSKiCFqkSkzK2nOQ4cYntYjut-gn8NU5vKYUBHviRs862dzZCryl5TwmXJ7mlQsmGMNLsBJO8kc_QISOtaBhn7PmT_QE6zvmK1CGYaql6iQ44azkXrDtEPy-TCdnG5F2Y8JTibZmxNUOJqemhGJyL8-tiCmQ8r94E3McA2JtU0WaE5G5gxB4yhGG-82apDeBPcklxOwyw1GmOYUxxggDZZexjApwjLnNV-25S2SouvEIvrFkyHD-sR-jb50-Xp-fNxdezL6cfL5pBUFoaMxBjBe1MJwVIJa21TJK2txyMMpRTygfZ9eNu1_U7pqgSZvsqeStaBePIj9CHve712nsYBwglmUVfJ1dN3elonP67Etysp3ijO8aVYrQKvHsQSPHHCrlo7_Jm1ASIa9asJaL-YNKSir79B72KawrV3j3FKKmalWJ7akgx5wT28TGU6C1svQ9b17D1fdha1qY3T208tvyOtgJ8D-RaChOkP3f_R_YXOqm45A</recordid><startdate>20200520</startdate><enddate>20200520</enddate><creator>Music, E.</creator><creator>Klein, T. 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J.</au><au>Lott, W. B.</au><au>Doran, M. R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-05-20</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>8340</spage><epage>8340</epage><pages>8340-8340</pages><artnum>8340</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>A previous study identified kartogenin (KGN) as a potent modulator of bone marrow mesenchymal stem/stromal cell (BMSC) chondrogenesis. This initial report did not contrast KGN directly against transforming growth factor-beta 1 (TGF-β1), the most common growth factor used in chondrogenic induction medium. Herein, we directly compared the
in vitro
chondrogenic potency of TGF-β1 and KGN using a high resolution micropellet model system. Micropellets were cultured for 7–14 days in medium supplemented with TGF-β1, KGN, or both TGF-β1 + KGN. Following 14 days of induction, micropellets exposed to TGF-β1 alone or TGF-β1 + KGN in combination were larger and produced more glycosominoglycan (GAG) than KGN-only cultures. When TGF-β1 + KGN was used, GAG quantities were similar or slightly greater than the TGF-β1-only cultures, depending on the BMSC donor. BMSC micropellet cultures supplemented with KGN alone contracted in size over the culture period and produced minimal GAG. Indicators of hypertrophy were not mitigated in TGF-β1 + KGN cultures, suggesting that KGN does not obstruct BMSC hypertrophy. KGN appears to have weak chondrogenic potency in human BMSC cultures relative to TGF-β1, does not obstruct hypertrophy, and may not be a viable alternative to growth factors in cartilage tissue engineering.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32433527</pmid><doi>10.1038/s41598-020-65283-8</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/532/1360 631/532/2074 692/308/2171 Anilides - pharmacology Bone growth Bone marrow Cartilage Cartilage - growth & development Cell culture Cell Differentiation - drug effects Cells, Cultured Chondrogenesis Chondrogenesis - drug effects Culture Media - pharmacology Growth factors Humanities and Social Sciences Humans Hypertrophy Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - physiology Mesenchyme multidisciplinary Phthalic Acids - pharmacology Physical growth Primary Cell Culture - methods Recombinant Proteins - pharmacology Science Science (multidisciplinary) Tissue engineering Tissue Engineering - methods Transforming Growth Factor beta1 - pharmacology Transforming growth factor-b1 |
| title | Transforming growth factor-beta stimulates human bone marrow-derived mesenchymal stem/stromal cell chondrogenesis more so than kartogenin |
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