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Verfasst von:Huck, Katrin [VerfasserIn]   i
 Zöller, Caren [VerfasserIn]   i
 Nakchbandi, Inaam [VerfasserIn]   i
Titel:The Rho GTPase RAC1 in Osteoblasts Controls Their Function
Verf.angabe:Katrin Huck, Carla Sens, Carina Wuerfel, Caren Zoeller, Inaam A. Nakchbandi
E-Jahr:2020
Jahr:8 January 2020
Umfang:16 S.
Fussnoten:Gesehen am 24.03.2020
Titel Quelle:Enthalten in: International journal of molecular sciences
Ort Quelle:Basel : Molecular Diversity Preservation International, 2000
Jahr Quelle:2020
Band/Heft Quelle:21(2020,2) Artikel-Nummer 385, 16 Seiten
ISSN Quelle:1422-0067
 1661-6596
Abstract:The regulation of the differentiation of the bone-forming cells, the osteoblasts, is complex. Many signaling pathways converge on the master regulator of osteoblast differentiation Runx2. The role of molecules that integrate several signaling pathways such as the Rho GTPases need to be better understood. We, therefore, asked at which stage Rac1, one of the Rho GTPase, is needed for osteoblast differentiation and whether it is involved in two pathways, the anabolic response to parathyroid hormone and the stimulatory effect of fibronectin isoforms on integrins. Genetic deletion of Rac1 in preosteoblasts using the osterix promoter diminished osteoblast differentiation in vitro. This effect was however similar to the presence of the promoter by itself. We, therefore, applied a Rac1 inhibitor and confirmed a decrease in differentiation. In vivo, Rac1 deletion using the osterix promoter decreased bone mineral density as well as histomorphometric measures of osteoblast function. In contrast, deleting Rac1 in differentiating osteoblasts using the collagen α1(I) promoter had no effects. We then evaluated whether intermittent parathyroid hormone (PTH) was able to affect bone mineral density in the absence of Rac1 in preosteoblasts. The increase in bone mineral density was similar in control animals and in mice in which Rac1 was deleted using the osterix promoter. Furthermore, stimulation of integrin by integrin isoforms was able to enhance osteoblast differentiation, despite the deletion of Rac1. In summary, Rac1 in preosteoblasts is required for normal osteoblast function and bone density, but it is neither needed for PTH-mediated anabolic effects nor for integrin-mediated enhancement of differentiation.
DOI:doi:10.3390/ijms21020385
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3390/ijms21020385
 Volltext: https://www.mdpi.com/1422-0067/21/2/385
 DOI: https://doi.org/10.3390/ijms21020385
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:169321394X
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