PMID- 28272338
OWN - NLM
STAT- MEDLINE
DCOM- 20170428
LR  - 20220408
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 3
DP  - 2017 Mar 7
TI  - Evidence of the Role of R-Spondin 1 and Its Receptor Lgr4 in the Transmission of 
      Mechanical Stimuli to Biological Signals for Bone Formation.
LID - 10.3390/ijms18030564 [doi]
LID - 564
AB  - 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/beta-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/beta-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/beta-catenin signaling for bone formation. Rspo1/Lgr4 could be a 
      new potential target for the prevention and treatment of disuse osteoporosis in 
      the future.
FAU - Shi, Gui-Xun
AU  - Shi GX
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. shiguixun@163.com.
FAU - Zheng, Xin-Feng
AU  - Zheng XF
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. zxf272@126.com.
FAU - Zhu, Chao
AU  - Zhu C
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. chaozhu007@126.com.
FAU - Li, Bo
AU  - Li B
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. libo6275819@126.com.
FAU - Wang, Yu-Ren
AU  - Wang YR
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. 13564869748@163.com.
FAU - Jiang, Sheng-Dan
AU  - Jiang SD
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. jiangsd@126.com.
FAU - Jiang, Lei-Sheng
AU  - Jiang LS
AD  - Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai 200092, China. jiangleisheng@xinhuamed.com.cn.
LA  - eng
PT  - Journal Article
DEP - 20170307
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (LGR4 protein, mouse)
RN  - 0 (RSPO1 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Thrombospondins)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Gene Expression Regulation
MH  - *Mechanotransduction, Cellular
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - Mice
MH  - *Osteogenesis
MH  - Receptors, G-Protein-Coupled/genetics/*metabolism
MH  - *Stress, Mechanical
MH  - Thrombospondins/genetics/*metabolism
MH  - Wnt Signaling Pathway
PMC - PMC5372580
OTO - NOTNLM
OT  - Lgr4
OT  - R-spondin 1
OT  - bone formation
OT  - bone mechanotransduction
OT  - osteoporosis
COIS- The authors declare no conflict of interest.
EDAT- 2017/03/09 06:00
MHDA- 2017/04/30 06:00
PMCR- 2017/03/01
CRDT- 2017/03/09 06:00
PHST- 2017/01/22 00:00 [received]
PHST- 2017/02/23 00:00 [revised]
PHST- 2017/02/28 00:00 [accepted]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2017/04/30 06:00 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - ijms18030564 [pii]
AID - ijms-18-00564 [pii]
AID - 10.3390/ijms18030564 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Mar 7;18(3):564. doi: 10.3390/ijms18030564.