Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages
Adipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell...
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/2190657 |
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| author | Laura Hyväri Miina Ojansivu Miia Juntunen Kimmo Kartasalo Susanna Miettinen Sari Vanhatupa |
| author_facet | Laura Hyväri Miina Ojansivu Miia Juntunen Kimmo Kartasalo Susanna Miettinen Sari Vanhatupa |
| author_sort | Laura Hyväri |
| collection | DOAJ |
| description | Adipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell adhesion and cytoskeleton have been suggested as central regulators of differentiation fate decision. However, the detailed knowledge of these molecular mechanisms in human ASCs remains limited. This study examined the significance of focal adhesion kinase (FAK), Rho-Rho-associated protein kinase (Rho-ROCK), and their downstream target extracellular signal-regulated kinase 1/2 (ERK1/2) on hASCs differentiation towards osteoblasts and adipocytes. Analyses of osteogenic markers RUNX2A, alkaline phosphatase, and matrix mineralization revealed an essential role of active FAK, ROCK, and ERK1/2 signaling for the osteogenesis of hASCs. Inhibition of these kinases with specific small molecule inhibitors diminished osteogenesis, while inhibition of FAK and ROCK activity led to elevation of adipogenic marker genes AP2 and LEP and lipid accumulation implicating adipogenesis. This denotes to a switch-like function of FAK and ROCK signaling in the osteogenic and adipogenic fates of hASCs. On the contrary, inhibition of ERK1/2 kinase activity deceased adipogenic differentiation, indicating that activation of ERK signaling is required for both adipogenic and osteogenic potential. Our findings highlight the reciprocal role of cell adhesion mechanisms and actin dynamics in regulation of hASC lineage commitment. This study enhances the knowledge of molecular mechanisms dictating hASC differentiation and thus opens possibilities for more efficient control of hASC differentiation. |
| format | Article |
| id | doaj-art-a9eb00ceefad4981806254d85dd77ed9 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-a9eb00ceefad4981806254d85dd77ed92025-02-03T01:33:23ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/21906572190657Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic LineagesLaura Hyväri0Miina Ojansivu1Miia Juntunen2Kimmo Kartasalo3Susanna Miettinen4Sari Vanhatupa5Adult Stem Cell Research Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandAdult Stem Cell Research Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandAdult Stem Cell Research Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandComputational Biology Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandAdult Stem Cell Research Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandAdult Stem Cell Research Group, BioMediTech Institute and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, FinlandAdipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell adhesion and cytoskeleton have been suggested as central regulators of differentiation fate decision. However, the detailed knowledge of these molecular mechanisms in human ASCs remains limited. This study examined the significance of focal adhesion kinase (FAK), Rho-Rho-associated protein kinase (Rho-ROCK), and their downstream target extracellular signal-regulated kinase 1/2 (ERK1/2) on hASCs differentiation towards osteoblasts and adipocytes. Analyses of osteogenic markers RUNX2A, alkaline phosphatase, and matrix mineralization revealed an essential role of active FAK, ROCK, and ERK1/2 signaling for the osteogenesis of hASCs. Inhibition of these kinases with specific small molecule inhibitors diminished osteogenesis, while inhibition of FAK and ROCK activity led to elevation of adipogenic marker genes AP2 and LEP and lipid accumulation implicating adipogenesis. This denotes to a switch-like function of FAK and ROCK signaling in the osteogenic and adipogenic fates of hASCs. On the contrary, inhibition of ERK1/2 kinase activity deceased adipogenic differentiation, indicating that activation of ERK signaling is required for both adipogenic and osteogenic potential. Our findings highlight the reciprocal role of cell adhesion mechanisms and actin dynamics in regulation of hASC lineage commitment. This study enhances the knowledge of molecular mechanisms dictating hASC differentiation and thus opens possibilities for more efficient control of hASC differentiation.http://dx.doi.org/10.1155/2018/2190657 |
| spellingShingle | Laura Hyväri Miina Ojansivu Miia Juntunen Kimmo Kartasalo Susanna Miettinen Sari Vanhatupa Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages Stem Cells International |
| title | Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages |
| title_full | Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages |
| title_fullStr | Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages |
| title_full_unstemmed | Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages |
| title_short | Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages |
| title_sort | focal adhesion kinase and rock signaling are switch like regulators of human adipose stem cell differentiation towards osteogenic and adipogenic lineages |
| url | http://dx.doi.org/10.1155/2018/2190657 |
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