NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells
Skeletal development and remodeling of adult bone are critically controlled by activated NOTCH signaling in genetically modified mice. It is yet unclear whether NOTCH signaling is activated by mechanical strain sensed by bone cells. We found that expression of specific NOTCH target genes is induced...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/5150634 |
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| author | Fani Ziouti Regina Ebert Maximilian Rummler Melanie Krug Sigrid Müller-Deubert Martin Lüdemann Franz Jakob Bettina M. Willie Franziska Jundt |
| author_facet | Fani Ziouti Regina Ebert Maximilian Rummler Melanie Krug Sigrid Müller-Deubert Martin Lüdemann Franz Jakob Bettina M. Willie Franziska Jundt |
| author_sort | Fani Ziouti |
| collection | DOAJ |
| description | Skeletal development and remodeling of adult bone are critically controlled by activated NOTCH signaling in genetically modified mice. It is yet unclear whether NOTCH signaling is activated by mechanical strain sensed by bone cells. We found that expression of specific NOTCH target genes is induced after in vivo tibial mechanical loading in wild-type mice. We further applied mechanical strain through cyclic stretching in human bone marrow-derived mesenchymal stromal cells (BMSCs) in vitro by using a bioreactor system and detected upregulation of NOTCH target gene expression. Inhibition of the NOTCH pathway in primary BMSCs as well as telomerase-immortalized human BMSCs (hMSC-TERT) through the gamma-secretase inhibitor GSI XII blocked mechanotransduction and modulated actin cytoskeleton organization. Short-hairpin RNA gene silencing identified NOTCH2 as the key receptor mediating NOTCH effects on hMSC-TERT cells. Our data indicate a functional link between NOTCH activation and mechanotransduction in human BMSCs. We suggest that NOTCH signaling is an important contributor to molecular mechanisms that mediate the bone formation response to mechanical strain. |
| format | Article |
| id | doaj-art-79d43e64571a4e6196e9e02fadec3477 |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-79d43e64571a4e6196e9e02fadec34772025-08-20T02:07:19ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/51506345150634NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal CellsFani Ziouti0Regina Ebert1Maximilian Rummler2Melanie Krug3Sigrid Müller-Deubert4Martin Lüdemann5Franz Jakob6Bettina M. Willie7Franziska Jundt8Department of Internal Medicine II and Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, GermanyOrthopedic Center for Musculoskeletal Research, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyResearch Centre, Shriners Hospital for Children-Canada, Department of Pediatric Surgery, McGill University, 1003 Decarie Blvd, Montreal, H4A 0A9, CanadaOrthopedic Center for Musculoskeletal Research, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyOrthopedic Center for Musculoskeletal Research, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyOrthopedic Center for Musculoskeletal Research, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyOrthopedic Center for Musculoskeletal Research, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyResearch Centre, Shriners Hospital for Children-Canada, Department of Pediatric Surgery, McGill University, 1003 Decarie Blvd, Montreal, H4A 0A9, CanadaDepartment of Internal Medicine II and Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, GermanySkeletal development and remodeling of adult bone are critically controlled by activated NOTCH signaling in genetically modified mice. It is yet unclear whether NOTCH signaling is activated by mechanical strain sensed by bone cells. We found that expression of specific NOTCH target genes is induced after in vivo tibial mechanical loading in wild-type mice. We further applied mechanical strain through cyclic stretching in human bone marrow-derived mesenchymal stromal cells (BMSCs) in vitro by using a bioreactor system and detected upregulation of NOTCH target gene expression. Inhibition of the NOTCH pathway in primary BMSCs as well as telomerase-immortalized human BMSCs (hMSC-TERT) through the gamma-secretase inhibitor GSI XII blocked mechanotransduction and modulated actin cytoskeleton organization. Short-hairpin RNA gene silencing identified NOTCH2 as the key receptor mediating NOTCH effects on hMSC-TERT cells. Our data indicate a functional link between NOTCH activation and mechanotransduction in human BMSCs. We suggest that NOTCH signaling is an important contributor to molecular mechanisms that mediate the bone formation response to mechanical strain.http://dx.doi.org/10.1155/2019/5150634 |
| spellingShingle | Fani Ziouti Regina Ebert Maximilian Rummler Melanie Krug Sigrid Müller-Deubert Martin Lüdemann Franz Jakob Bettina M. Willie Franziska Jundt NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells Stem Cells International |
| title | NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_full | NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_fullStr | NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_full_unstemmed | NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_short | NOTCH Signaling Is Activated through Mechanical Strain in Human Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_sort | notch signaling is activated through mechanical strain in human bone marrow derived mesenchymal stromal cells |
| url | http://dx.doi.org/10.1155/2019/5150634 |
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