Context-Specific Osteogenic Potential of Mesenchymal Stem Cells
Despite the great progress in the field of bone tissue regeneration, the early initiating mechanisms of osteogenic differentiation are not well understood. Cells capable of osteogenic transformation vary from mesenchymal stem cells of various origins to mural cells of vessels. The mechanisms of path...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/6/673 |
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| author | Aleksandra Kostina Arseniy Lobov Daria Semenova Artem Kiselev Polina Klausen Anna Malashicheva |
| author_facet | Aleksandra Kostina Arseniy Lobov Daria Semenova Artem Kiselev Polina Klausen Anna Malashicheva |
| author_sort | Aleksandra Kostina |
| collection | DOAJ |
| description | Despite the great progress in the field of bone tissue regeneration, the early initiating mechanisms of osteogenic differentiation are not well understood. Cells capable of osteogenic transformation vary from mesenchymal stem cells of various origins to mural cells of vessels. The mechanisms of pathological calcification are thought to be similar to those of bone formation. Notch signaling has been shown to play an important role in osteogenic differentiation, as well as in pathological calcification. Nevertheless, despite its known tissue- and context-specificity, the information about its role in the osteogenic differentiation of different cells is still limited. We compared mesenchymal stem cells from adipogenic tissue (MSCs) and interstitial cells from the aortic valve (VICs) by their ability to undergo Notch-dependent osteogenic differentiation. We showed differences between the two types of cells in their ability to activate the expression of proosteogenic genes <i>RUNX2</i>, <i>BMP2</i>, <i>BMP4</i>, <i>DLX2</i>, <i>BGLAP</i>, <i>SPRY</i>, <i>IBSP</i>, and <i>SPP1</i> in response to Notch activation. Untargeted metabolomic profiling also confirms differences between MSCs and VICs in their osteogenic state. Analysis of the activity of <i>RUNX2</i> and <i>SPP1</i> promoters shows fine-tuned dose-dependency in response to Notch induction and suggests a direct link between the level of Notch activation, and the proostogenic gene expression and corresponding osteogenic induction. Our data suggest that osteogenic differentiation is a context-dependent process and the outcome of it could be cell-type dependent. |
| first_indexed | 2024-03-10T10:27:20Z |
| format | Article |
| id | doaj.art-6a64a73297e7454484d7a6a052325060 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T10:27:20Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-6a64a73297e7454484d7a6a0523250602023-11-21T23:53:11ZengMDPI AGBiomedicines2227-90592021-06-019667310.3390/biomedicines9060673Context-Specific Osteogenic Potential of Mesenchymal Stem CellsAleksandra Kostina0Arseniy Lobov1Daria Semenova2Artem Kiselev3Polina Klausen4Anna Malashicheva5Laboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaLaboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaLaboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaLaboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaLaboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaLaboratory of Regenerative Biomedicine, Institute of Cytology Russian Academy of Science, 194064 Saint Petersburg, RussiaDespite the great progress in the field of bone tissue regeneration, the early initiating mechanisms of osteogenic differentiation are not well understood. Cells capable of osteogenic transformation vary from mesenchymal stem cells of various origins to mural cells of vessels. The mechanisms of pathological calcification are thought to be similar to those of bone formation. Notch signaling has been shown to play an important role in osteogenic differentiation, as well as in pathological calcification. Nevertheless, despite its known tissue- and context-specificity, the information about its role in the osteogenic differentiation of different cells is still limited. We compared mesenchymal stem cells from adipogenic tissue (MSCs) and interstitial cells from the aortic valve (VICs) by their ability to undergo Notch-dependent osteogenic differentiation. We showed differences between the two types of cells in their ability to activate the expression of proosteogenic genes <i>RUNX2</i>, <i>BMP2</i>, <i>BMP4</i>, <i>DLX2</i>, <i>BGLAP</i>, <i>SPRY</i>, <i>IBSP</i>, and <i>SPP1</i> in response to Notch activation. Untargeted metabolomic profiling also confirms differences between MSCs and VICs in their osteogenic state. Analysis of the activity of <i>RUNX2</i> and <i>SPP1</i> promoters shows fine-tuned dose-dependency in response to Notch induction and suggests a direct link between the level of Notch activation, and the proostogenic gene expression and corresponding osteogenic induction. Our data suggest that osteogenic differentiation is a context-dependent process and the outcome of it could be cell-type dependent.https://www.mdpi.com/2227-9059/9/6/673Notchosteogenic differentiationmesenchymal stem cellsaortic valve interstitial cellscalcification |
| spellingShingle | Aleksandra Kostina Arseniy Lobov Daria Semenova Artem Kiselev Polina Klausen Anna Malashicheva Context-Specific Osteogenic Potential of Mesenchymal Stem Cells Biomedicines Notch osteogenic differentiation mesenchymal stem cells aortic valve interstitial cells calcification |
| title | Context-Specific Osteogenic Potential of Mesenchymal Stem Cells |
| title_full | Context-Specific Osteogenic Potential of Mesenchymal Stem Cells |
| title_fullStr | Context-Specific Osteogenic Potential of Mesenchymal Stem Cells |
| title_full_unstemmed | Context-Specific Osteogenic Potential of Mesenchymal Stem Cells |
| title_short | Context-Specific Osteogenic Potential of Mesenchymal Stem Cells |
| title_sort | context specific osteogenic potential of mesenchymal stem cells |
| topic | Notch osteogenic differentiation mesenchymal stem cells aortic valve interstitial cells calcification |
| url | https://www.mdpi.com/2227-9059/9/6/673 |
| work_keys_str_mv | AT aleksandrakostina contextspecificosteogenicpotentialofmesenchymalstemcells AT arseniylobov contextspecificosteogenicpotentialofmesenchymalstemcells AT dariasemenova contextspecificosteogenicpotentialofmesenchymalstemcells AT artemkiselev contextspecificosteogenicpotentialofmesenchymalstemcells AT polinaklausen contextspecificosteogenicpotentialofmesenchymalstemcells AT annamalashicheva contextspecificosteogenicpotentialofmesenchymalstemcells |