| |  Online-Ressource |
|---|
| Verfasst von: | Zaloszyc, Ariane [VerfasserIn]  |
|---|
| | Choquet, Philippe [VerfasserIn] |
|---|
| | Sayeh, Amira [VerfasserIn] |
|---|
| | Bartosova, Maria [VerfasserIn] |
|---|
| | Schäfer, Betti [VerfasserIn] |
|---|
| | Huegel, Ulrike [VerfasserIn] |
|---|
| | Aubertin-Kirch, Gaëlle [VerfasserIn] |
|---|
| | Healy, Christopher [VerfasserIn] |
|---|
| | Severac, François [VerfasserIn] |
|---|
| | Rizzo, Sébastien [VerfasserIn] |
|---|
| | Boivin, Georges [VerfasserIn] |
|---|
| | Schaefer, Franz [VerfasserIn] |
|---|
| | Fischbach, Michel [VerfasserIn] |
|---|
| | Bacchetta, Justine [VerfasserIn] |
|---|
| | Bahram, Seiamak [VerfasserIn] |
|---|
| | Schmitt, Claus P. [VerfasserIn] |
|---|
| Titel: | Inactivation of osteoblast PKC signaling reduces cortical bone mass and density and aggravates renal osteodystrophy in mice with chronic kidney disease on high phosphate diet |
|---|
| Verf.angabe: | Ariane Zaloszyc, Philippe Choquet, Amira Sayeh, Maria Bartosova, Betti Schaefer, Ulrike Huegel, Gaëlle Aubertin-Kirch, Christopher Healy, François Severac, Sébastien Rizzo, Georges Boivin, Franz Schaefer, Michel Fischbach, Justine Bacchetta, Seiamak Bahram and Claus Peter Schmitt |
|---|
| E-Jahr: | 2022 |
|---|
| Jahr: | 8 June 2022 |
|---|
| Umfang: | 14 S. |
|---|
| Fussnoten: | Gesehen am 06.07.2022 |
|---|
| Titel Quelle: | Enthalten in: International journal of molecular sciences |
|---|
| Ort Quelle: | Basel : Molecular Diversity Preservation International, 2000 |
|---|
| Jahr Quelle: | 2022 |
|---|
| Band/Heft Quelle: | 23(2022), 12, Artikel-ID 6404, Seite 1-14 |
|---|
| ISSN Quelle: | 1422-0067 |
|---|
| | 1661-6596 |
|---|
| Abstract: | Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease. |
|---|
| DOI: | doi:10.3390/ijms23126404 |
|---|
| URL: | kostenfrei: Volltext ; Verlag: https://doi.org/10.3390/ijms23126404 |
|---|
| | kostenfrei: Volltext: https://www.mdpi.com/1422-0067/23/12/6404 |
|---|
| | DOI: https://doi.org/10.3390/ijms23126404 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| Sach-SW: | bone scintigraphy |
|---|
| | bone μCT |
|---|
| | CKD-MBD |
|---|
| | parathyroid related disorder |
|---|
| | preclinical studies |
|---|
| K10plus-PPN: | 1809326419 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
| |
|
|---|
| | |
|---|
| Lokale URL UB: |  Zum Volltext |
|---|
Inactivation of osteoblast PKC signaling reduces cortical bone mass and density and aggravates renal osteodystrophy in mice with chronic kidney disease on high phosphate diet / Zaloszyc, Ariane [VerfasserIn]; 8 June 2022 (Online-Ressource)
