Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells
Bone marrow-derived mesenchymal stromal cells (hMSCs) are capable of differentiating into the osteogenic lineage, and for osteogenic differentiation, mechanical loading is a relevant stimulus. Mechanotransduction leads to the formation of second messengers such as cAMP, cGMP, or Ca2+ influx resultin...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/7865484 |
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| author | Sigrid Müller-Deubert Carolin Ege Melanie Krug Jutta Meißner-Weigl Maximilian Rudert Oliver Bischof Franz Jakob Regina Ebert |
| author_facet | Sigrid Müller-Deubert Carolin Ege Melanie Krug Jutta Meißner-Weigl Maximilian Rudert Oliver Bischof Franz Jakob Regina Ebert |
| author_sort | Sigrid Müller-Deubert |
| collection | DOAJ |
| description | Bone marrow-derived mesenchymal stromal cells (hMSCs) are capable of differentiating into the osteogenic lineage, and for osteogenic differentiation, mechanical loading is a relevant stimulus. Mechanotransduction leads to the formation of second messengers such as cAMP, cGMP, or Ca2+ influx resulting in the activation of transcription factors mediating gene regulation. The second messengers cAMP and cGMP are degraded by phosphodiesterase isoenzymes (PDE), but the role of these enzymes during osteogenic differentiation or mechanotransduction remains unclear. Here, we focused on the isoenzyme phosphodiesterase 10A (PDE10A) and its role during osteogenic commitment and mechanotransduction. We observed a time-dependent decrease of PDE10A expression in hMSC undergoing differentiation towards the osteogenic lineage. PDE10A inhibition by papaverine diminished osteogenic differentiation. While applying mechanical strain via cyclic stretching of hMSCs led to an upregulation of PDE10A gene expression, inhibition of PDE10A using the drug papaverine repressed expression of mechanoresponsive genes. We conclude that PDE10A is a modulator of osteogenic differentiation as well as mechanotransduction in hMSCs. Our data further suggests that the relative increase of cAMP, rather than the absolute cAMP level, is a key driver of the observed effects. |
| format | Article |
| id | doaj-art-78cb158211b14f0292a8b3570523eaae |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-78cb158211b14f0292a8b3570523eaae2025-02-03T06:46:28ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/78654847865484Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal CellsSigrid Müller-Deubert0Carolin Ege1Melanie Krug2Jutta Meißner-Weigl3Maximilian Rudert4Oliver Bischof5Franz Jakob6Regina Ebert7Bernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyInstitute Pasteur, Department of Cell Biology and Infection, 25-28 Rue du Docteur Roux, 75015 Paris, FranceBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBernhard Heine Center for Locomotion Research, Orthopedic Department, University of Würzburg, Friedrich-Bergius-Ring 15, 97076 Würzburg, GermanyBone marrow-derived mesenchymal stromal cells (hMSCs) are capable of differentiating into the osteogenic lineage, and for osteogenic differentiation, mechanical loading is a relevant stimulus. Mechanotransduction leads to the formation of second messengers such as cAMP, cGMP, or Ca2+ influx resulting in the activation of transcription factors mediating gene regulation. The second messengers cAMP and cGMP are degraded by phosphodiesterase isoenzymes (PDE), but the role of these enzymes during osteogenic differentiation or mechanotransduction remains unclear. Here, we focused on the isoenzyme phosphodiesterase 10A (PDE10A) and its role during osteogenic commitment and mechanotransduction. We observed a time-dependent decrease of PDE10A expression in hMSC undergoing differentiation towards the osteogenic lineage. PDE10A inhibition by papaverine diminished osteogenic differentiation. While applying mechanical strain via cyclic stretching of hMSCs led to an upregulation of PDE10A gene expression, inhibition of PDE10A using the drug papaverine repressed expression of mechanoresponsive genes. We conclude that PDE10A is a modulator of osteogenic differentiation as well as mechanotransduction in hMSCs. Our data further suggests that the relative increase of cAMP, rather than the absolute cAMP level, is a key driver of the observed effects.http://dx.doi.org/10.1155/2020/7865484 |
| spellingShingle | Sigrid Müller-Deubert Carolin Ege Melanie Krug Jutta Meißner-Weigl Maximilian Rudert Oliver Bischof Franz Jakob Regina Ebert Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells Stem Cells International |
| title | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_full | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_fullStr | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_full_unstemmed | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_short | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
| title_sort | phosphodiesterase 10a is a mediator of osteogenic differentiation and mechanotransduction in bone marrow derived mesenchymal stromal cells |
| url | http://dx.doi.org/10.1155/2020/7865484 |
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