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  The Rho GTPase RAC1 in osteoblasts controls their function

Huck, K., Sens, C., Wuerfel, C., Zoeller, C., & Nakchbandi, I. A. (2020). The Rho GTPase RAC1 in osteoblasts controls their function. International Journal of Molecular Sciences, 21(2): 385, pp. 1-16. doi:10.3390/ijms21020385.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-7BF1-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-7BF2-0
Genre: Journal Article

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 Creators:
Huck , Katrin, Author
Sens, Carla, Author
Wuerfel, Carina, Author
Zoeller , Caren, Author
Nakchbandi, Inaam A.1, Author              
Affiliations:
1Max Planck Institute for Medical Research, Max Planck Society, ou_1125545              

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Free keywords: preosteoblast; osteoblast; differentiation; Rac1; Rho GTPase; PTH; parathyroid hormone; integrin; ERK; AKT; fibronectin; EDA fibronectin; EDB fibronectin; anabolic
 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.

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Language(s): eng - English
 Dates: 2019-10-312019-12-312020-01-08
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.3390/ijms21020385
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Title: International Journal of Molecular Sciences
  Abbreviation : Int. J. Mol. Sci.
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI AG
Pages: - Volume / Issue: 21 (2) Sequence Number: 385 Start / End Page: 1 - 16 Identifier: ISSN: 1422-0067
CoNE: https://pure.mpg.de/cone/journals/resource/1422-0067