Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells
| العنوان: | Phosphodiesterase 10A Is a Mediator of Osteogenic Differentiation and Mechanotransduction in Bone Marrow-Derived Mesenchymal Stromal Cells |
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| المؤلفون: | Franz Jakob, Maximilian Rudert, Sigrid Müller-Deubert, Regina Ebert, Oliver Bischof, Jutta Meißner-Weigl, Melanie Krug, Carolin Ege |
| المساهمون: | Center for Locomotion Research - Lehrstuhl für Orthopädie, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Département de Biologie cellulaire et infection - Department of Cell Biology and infection (BCI), Institut Pasteur [Paris], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Bundesministerium für Bil-dung und Forschung (BMBF) grant 01EC1402C (DIMEOs)and by the Europäischer Fonds für regionale Entwicklung(EFRE) grant EU-1650-0006 to F. Jakob and by the DeutscheForschungsgemeinschaft (DFG, German Research Founda-tion)-Projektnummer 326998133-TRR 225 (subproject B05,R. Ebert)., Julius-Maximilians-Universität Würzburg (JMU), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Stem Cells International Stem Cells International, Hindawi Publishing Corporation, 2020, 2020, pp.1-11. ⟨10.1155/2020/7865484⟩ Stem Cells International, Vol 2020 (2020) Stem Cells International, 2020, 2020, pp.1-11. ⟨10.1155/2020/7865484⟩ |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Regulation of gene expression, 0303 health sciences, Article Subject, Chemistry, [SDV]Life Sciences [q-bio], Mesenchymal stem cell, Phosphodiesterase, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, RC31-1245, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, 030220 oncology & carcinogenesis, Gene expression, Second messenger system, PDE10A, Mechanotransduction, Molecular Biology, Internal medicine, 030304 developmental biology, Research Article |
| الوصف: | 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. |
| وصف الملف: | text/xhtml |
| اللغة: | English |
| تدمد: | 1687-966X 1687-9678 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::779b7ce44fa5290f25015a5571943661 https://hal.archives-ouvertes.fr/hal-03045549/document |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....779b7ce44fa5290f25015a5571943661 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1687966X 16879678 |
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