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RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss

Overview of attention for article published in Cell Regeneration, March 2021
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Title
RhoA/Rock activation represents a new mechanism for inactivating Wnt/β-catenin signaling in the aging-associated bone loss
Published in
Cell Regeneration, March 2021
DOI 10.1186/s13619-020-00071-3
Pubmed ID
Authors

Wei Shi, Chengyun Xu, Ying Gong, Jirong Wang, Qianlei Ren, Ziyi Yan, Liu Mei, Chao Tang, Xing Ji, Xinhua Hu, Meiyu Qv, Musaddique Hussain, Ling-Hui Zeng, Ximei Wu

Abstract

The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis, whereas nuclear accumulation of β-catenin requires the activation of Rac1, a member of the Rho small GTPase family. The aim of the present study was to investigate the role of RhoA/Rho kinase (Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss. We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3β at Tyr216, resulting in Gsk3β activation and subsequent β-catenin destabilization. In line with these molecular events, RhoA loss- or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion of β-catenin, respectively. Likewise, RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it. Importantly, high RhoA/Rock activity closely correlates with Jak and Gsk3β activities but inversely correlates with β-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice, whereas systemic inhibition of Rock therefore activates the β-catenin signaling to antagonize aging-associated bone loss. Taken together, these results identify RhoA/Rock-dependent Gsk3β activation and subsequent β-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.

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Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 20%
Student > Ph. D. Student 2 13%
Student > Bachelor 2 13%
Student > Master 2 13%
Unknown 6 40%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 33%
Arts and Humanities 1 7%
Neuroscience 1 7%
Chemistry 1 7%
Medicine and Dentistry 1 7%
Other 0 0%
Unknown 6 40%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 August 2022.
All research outputs
#18,687,330
of 23,153,849 outputs
Outputs from Cell Regeneration
#113
of 156 outputs
Outputs of similar age
#316,131
of 419,532 outputs
Outputs of similar age from Cell Regeneration
#5
of 11 outputs
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So far Altmetric has tracked 156 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 2nd percentile – i.e., 2% of its peers scored the same or lower than it.
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We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.