Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis.
Human mesenchymal stem cells (hMSCs) are multipotent cells capable of differentiating into a variety of mature cell types, including osteoblasts, adipocytes and chondrocytes. It has previously been shown that, when expanded in medium supplemented with fibroblast growth factor-2 (FGF-2), hMSCs show e...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3144950?pdf=render |
| _version_ | 1819050819244261376 |
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| author | Andrew M Handorf Wan-Ju Li |
| author_facet | Andrew M Handorf Wan-Ju Li |
| author_sort | Andrew M Handorf |
| collection | DOAJ |
| description | Human mesenchymal stem cells (hMSCs) are multipotent cells capable of differentiating into a variety of mature cell types, including osteoblasts, adipocytes and chondrocytes. It has previously been shown that, when expanded in medium supplemented with fibroblast growth factor-2 (FGF-2), hMSCs show enhanced chondrogenesis (CG). Previous work concluded that the enhancement of CG could be attributed to the selection of a cell subpopulation with inherent chondrogenic potential. In this study, we show that FGF-2 pretreatment actually primed hMSCs to undergo enhanced CG by increasing basal Sox9 protein levels. Our results show that Sox9 protein levels were elevated within 30 minutes of exposure to FGF-2 and progressively increased with longer exposures. Further, we show using flow cytometry that FGF-2 increased Sox9 protein levels per cell in proliferating and non-proliferating hMSCs, strongly suggesting that FGF-2 primes hMSCs for subsequent CG by regulating Sox9. Indeed, when hMSCs were exposed to FGF-2 for 2 hours and subsequently differentiated into the chondrogenic lineage using pellet culture, phosphorylated-Sox9 (pSox9) protein levels became elevated and ultimately resulted in an enhancement of CG. However, small interfering RNA (siRNA)-mediated knockdown of Sox9 during hMSC expansion was unable to negate the prochondrogenic effects of FGF-2, suggesting that the FGF-2-mediated enhancement of hMSC CG is only partly regulated through Sox9. Our findings provide new insights into the mechanism by which FGF-2 regulates predifferentiation hMSCs to undergo enhanced CG. |
| first_indexed | 2024-12-21T11:54:06Z |
| format | Article |
| id | doaj.art-6d15c577a9164a7c97d47289a0168628 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T11:54:06Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-6d15c577a9164a7c97d47289a01686282022-12-21T19:04:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2288710.1371/journal.pone.0022887Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis.Andrew M HandorfWan-Ju LiHuman mesenchymal stem cells (hMSCs) are multipotent cells capable of differentiating into a variety of mature cell types, including osteoblasts, adipocytes and chondrocytes. It has previously been shown that, when expanded in medium supplemented with fibroblast growth factor-2 (FGF-2), hMSCs show enhanced chondrogenesis (CG). Previous work concluded that the enhancement of CG could be attributed to the selection of a cell subpopulation with inherent chondrogenic potential. In this study, we show that FGF-2 pretreatment actually primed hMSCs to undergo enhanced CG by increasing basal Sox9 protein levels. Our results show that Sox9 protein levels were elevated within 30 minutes of exposure to FGF-2 and progressively increased with longer exposures. Further, we show using flow cytometry that FGF-2 increased Sox9 protein levels per cell in proliferating and non-proliferating hMSCs, strongly suggesting that FGF-2 primes hMSCs for subsequent CG by regulating Sox9. Indeed, when hMSCs were exposed to FGF-2 for 2 hours and subsequently differentiated into the chondrogenic lineage using pellet culture, phosphorylated-Sox9 (pSox9) protein levels became elevated and ultimately resulted in an enhancement of CG. However, small interfering RNA (siRNA)-mediated knockdown of Sox9 during hMSC expansion was unable to negate the prochondrogenic effects of FGF-2, suggesting that the FGF-2-mediated enhancement of hMSC CG is only partly regulated through Sox9. Our findings provide new insights into the mechanism by which FGF-2 regulates predifferentiation hMSCs to undergo enhanced CG.http://europepmc.org/articles/PMC3144950?pdf=render |
| spellingShingle | Andrew M Handorf Wan-Ju Li Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. PLoS ONE |
| title | Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. |
| title_full | Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. |
| title_fullStr | Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. |
| title_full_unstemmed | Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. |
| title_short | Fibroblast growth factor-2 primes human mesenchymal stem cells for enhanced chondrogenesis. |
| title_sort | fibroblast growth factor 2 primes human mesenchymal stem cells for enhanced chondrogenesis |
| url | http://europepmc.org/articles/PMC3144950?pdf=render |
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