β-Arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice

Pierroz, Dominique D., Rufo, Anna, Bianchi, Estelle N., Glatt, Vaida, Capulli, Mattia, Rucci, Nadia, Cavat, Fanny, Rizzoli, René, Teti, Anna, Bouxsein, Mary L., & Ferrari, Serge L. (2009) β-Arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice. Journal of Bone and Mineral Research, 24(5), pp. 775-784.

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Abstract

PTH-stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule barrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in b-arrestin22/2 mice and suggested that b-arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of b-arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and barrestin2 2/2 mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH-stimulated OCs was higher in BM cultures from b-arrestin22/2 compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in b-arrestin22/2 compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in b-arrestin22/2. PTH downregulated Efn and Eph genes in b-arrestin22/2, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in b-arrestin22/2 compared with WT. Histomorphometry showed that OC number was higher in OVX-b-arrestin22/2 compared with WT. These results indicate that b-arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, b-arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation.

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25 citations in Scopus
22 citations in Web of Science®
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ID Code: 70873
Item Type: Journal Article
Refereed: Yes
Keywords: b-arrestin2, RANKL, ephrin, low calcium diet, bone remodeling
DOI: 10.1359/JBMR.081237
ISSN: 0884-0431
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2009 American Society for Bone and Mineral Research
Deposited On: 02 May 2014 02:17
Last Modified: 02 Jun 2014 01:11

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