Next Article in Journal
Alternative Splicing of hTERT Pre-mRNA: A Potential Strategy for the Regulation of Telomerase Activity
Next Article in Special Issue
Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss
Previous Article in Journal
Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation
Previous Article in Special Issue
Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 564; doi:10.3390/ijms18030564

Evidence of the Role of R-Spondin 1 and Its Receptor Lgr4 in the Transmission of Mechanical Stimuli to Biological Signals for Bone Formation

Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
*
Author to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 22 January 2017 / Revised: 23 February 2017 / Accepted: 28 February 2017 / Published: 7 March 2017
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
View Full-Text   |   Download PDF [4017 KB, uploaded 7 March 2017]   |  

Abstract

The bone can adjust its mass and architecture to mechanical stimuli via a series of molecular cascades, which have been not yet fully elucidated. Emerging evidence indicated that R-spondins (Rspos), a family of secreted agonists of the Wnt/β-catenin signaling pathway, had important roles in osteoblastic differentiation and bone formation. However, the role of Rspo proteins in mechanical loading-influenced bone metabolism has never been investigated. In this study, we found that Rspo1 was a mechanosensitive protein for bone formation. Continuous cyclic mechanical stretch (CMS) upregulated the expression of Rspo1 in mouse bone marrow mesenchymal stem cells (BMSCs), while the expression of Rspo1 in BMSCs in vivo was downregulated in the bones of a mechanical unloading mouse model (tail suspension (TS)). On the other hand, Rspo1 could promote osteogenesis of BMSCs under CMS through activating the Wnt/β-catenin signaling pathway and could rescue the bone loss induced by mechanical unloading in the TS mice. Specifically, our results suggested that Rspo1 and its receptor of leucine-rich repeat containing G-protein-coupled receptor 4 (Lgr4) should be a novel molecular signal in the transmission of mechanical stimuli to biological signal in the bone, and this signal should be in the upstream of Wnt/β-catenin signaling for bone formation. Rspo1/Lgr4 could be a new potential target for the prevention and treatment of disuse osteoporosis in the future. View Full-Text
Keywords: R-spondin 1; Lgr4; bone formation; bone mechanotransduction; osteoporosis R-spondin 1; Lgr4; bone formation; bone mechanotransduction; osteoporosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Shi, G.-X.; Zheng, X.-F.; Zhu, C.; Li, B.; Wang, Y.-R.; Jiang, S.-D.; Jiang, L.-S. Evidence of the Role of R-Spondin 1 and Its Receptor Lgr4 in the Transmission of Mechanical Stimuli to Biological Signals for Bone Formation. Int. J. Mol. Sci. 2017, 18, 564.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top