Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells
Author Manuscript 2011 April 29.
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2012
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| Online Access: | http://hdl.handle.net/1721.1/75758 https://orcid.org/0000-0002-1801-5548 |
| _version_ | 1811090732144918528 |
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| author | Platt, Manu O. Roman, Arian J. Wells, Alan Lauffenburger, Douglas A. Griffith, Linda G. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Platt, Manu O. Roman, Arian J. Wells, Alan Lauffenburger, Douglas A. Griffith, Linda G. |
| author_sort | Platt, Manu O. |
| collection | MIT |
| description | Author Manuscript 2011 April 29. |
| first_indexed | 2024-09-23T14:51:05Z |
| format | Article |
| id | mit-1721.1/75758 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:51:05Z |
| publishDate | 2012 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/757582022-09-29T10:56:41Z Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells Platt, Manu O. Roman, Arian J. Wells, Alan Lauffenburger, Douglas A. Griffith, Linda G. Massachusetts Institute of Technology. Department of Biological Engineering Platt, Manu O. Roman, Arian J. Lauffenburger, Douglas A. Griffith, Linda G. Author Manuscript 2011 April 29. Epidermal growth factor receptor (EGFR)-mediated signaling helps regulate bone development and healing through its effects on osteogenic cells. Here, we show how EGFR activity and osteogenic differentiation responses in primary human bone marrow-derived multipotent stromal cells (MSCs) are influenced by presenting covalently tethered epidermal growth factor (tEGF) on the culture substratum, a presentation mode that reduces EGFR internalization and restricts signaling to the cell surface. In both absence and presence of tEGF, MSCs increase expression levels of EGFR and its heterodimerization partner HER2 during the course of osteogenic differentiation. tEGF substrata increased levels of phosphorylated EGFR and phosphorylated extracellular regulated kinase (ERK) compared to control substrata, and these elevations were associated with a twofold enhancement of MSC alkaline phosphatase activity at day 7 and matrix mineralization at day 21. Surprisingly, addition of soluble EGF (sEGF) to cells cultured on tEGF substrata reduces osteogenic differentiation, even though EGFR signaling is more strongly activated in acute, short-term manner by sEGF treatment than by tEGF treatment. A striking concomitant result of the sEGF effects is near-complete downregulation of EGFR and HER2, demonstrating that the tEGF/EGFR interaction is dynamically reversible even though temporally sustained. Taken together, our results show that enhanced MSC osteogenic differentiation corresponds to a sustained combination of receptor expression and ligand presentation, both of which are maintained by tEGF. National Institutes of Health (U.S.) (Grant R01-GM059870-07) National Institutes of Health (U.S.) (Grant R01-DE 019523-10) National Institutes of Health (U.S.) (Grant P40RR017447) United Negro College Fund (Merck Postdoctoral Fellowship) Georgia Institute of Technology (FACES Fellowship) National Center for Research Resources (U.S.) (Grant P40RR017447) 2012-12-18T15:12:49Z 2012-12-18T15:12:49Z 2009-06 2008-12 Article http://purl.org/eprint/type/JournalArticle 0021-9541 1097-4652 http://hdl.handle.net/1721.1/75758 Platt, Manu O. et al. “Sustained Epidermal Growth Factor Receptor Levels and Activation by Tethered Ligand Binding Enhances Osteogenic Differentiation of Multi-potent Marrow Stromal Cells.” Journal of Cellular Physiology 221.2 (2009): 306–317. https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1002/jcp.21854 Journal of Cellular Physiology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Platt, Manu O. Roman, Arian J. Wells, Alan Lauffenburger, Douglas A. Griffith, Linda G. Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title | Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title_full | Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title_fullStr | Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title_full_unstemmed | Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title_short | Sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi-potent marrow stromal cells |
| title_sort | sustained epidermal growth factor receptor levels and activation by tethered ligand binding enhances osteogenic differentiation of multi potent marrow stromal cells |
| url | http://hdl.handle.net/1721.1/75758 https://orcid.org/0000-0002-1801-5548 |
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