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Rspo1 promotes osteoblast differentiation via Wnt signaling pathway

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Title Rspo1 promotes osteoblast differentiation via Wnt signaling pathway
 
Creator Sharma, Ashish R
Choi, Byung-Soo
Park, Jong-Min
Lee, Dong-Hyun
Lee, Jeong-Eun
Kim, Hae-Sung
Yoon, Jeong-Kyo
Song, Dong-Keun
Nam, Ju-Suk
Lee, Sang-Soo
 
Subject Rspo1
Wnt signaling
Osteoblast
β-Catenin
 
Description 19-25
R-spondin (Rspo)s proteins are a new group
of Wnt/beta-catenin signaling agonists. These signaling molecules are known to
be involved in the developmental stages of skeletal system. Recent studies in
various murine osteoblast models have proposed that Rspo1 may interact with Wnt
signaling pathway to induce differentiation in osteoblasts. Though findings in
murine osteoblasts implicate a synergestic role of Rspo1 with Wnt signaling,
still no study has addressed the similar role in more clinically applicable
osteoblast models i.e., human cell lines or primary cells. Therefore, in the
present study, we investigated the possible role of Rspo1 during
differentiation process of human in vitro
osteoblast cell models like primary osteoblasts or human osteoprogenitor cell
line hFOB1.19 along with murine preosteoblast cell line MC3T3 E-1. Our results
showed increase in Rspo1 at transcript level during differentiating phase of human
primary osteoblasts and human FOB1.19 cells. We also found that Rspo1 (100
ng/mL) acts additively with Wnt3a to activate Wnt signaling, as confirmed by
luciferase activity after transfection of TOPFLASH construct to hFOB1.19 cells.
Similar additive role of Rspo1 and Wnt3a was apparent in alkaline phosphatase
(ALP) activity analysis of human primary cells. Moreover, a reduction in ALP
activity was observed with knock-down of Rspo1 by transfected shRNA in hFOB1.19
cells. These results suggested the possibility of autocrine regulation by Rspo1
on the osteogenic activities in human in
vitro osteoblast models. Furthermore, these results were corroborated in
MC3T3-E1, murine osteoblast cell model. Osteoblastic differentiation was
induced by transfection of Rspo1 which was confirmed by increased ALP staining and qRT-PCR analysis of osteogenic markers, such as Runx2 and osteocalcin. In conclusion, present study highlights the role of Rspo1 in bone remodeling where
it activates Wnt signaling to induce differentiation, as shown in human as well murine in vitro
osteoblast cell models.
 
Date 2013-02-23T11:24:18Z
2013-02-23T11:24:18Z
2013-02
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/16062
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.50(1) [February 2013]