scholarly journals Wnt Signaling and Genetic Bone Diseases

2019 ◽  
Author(s):  
Yanqin Lu ◽  
Jinxiang Han
Keyword(s):  
Wnt Signaling ◽  
Bone Diseases

scholarly journals Analysis of Endogenous LRP6 Function Reveals a Novel Feedback Mechanism by Which Wnt Negatively Regulates Its Receptor

2007 ◽  
Vol 27 (20) ◽  
pp. 7291-7301 ◽  
Author(s):  
Zahid Khan ◽  
Sapna Vijayakumar ◽  
Teresa Villanueva de la Torre ◽  
Sabrina Rotolo ◽  
Anna Bafico
Keyword(s):  
Wnt Signaling ◽  
Wnt Pathway ◽  
Mrna Level ◽  
Cellular Membrane ◽  
Feedback Mechanism ◽  
Bone Diseases ◽  
Dependent Manner ◽  
Direct Role ◽  
Initial Stimulus ◽  
Canonical Wnt

ABSTRACT The canonical Wnt pathway plays a crucial role in embryonic development, and its deregulation is involved in human diseases. The LRP6 single-span transmembrane coreceptor is essential for transmission of canonical Wnt signaling. However, due to the lack of immunological reagents, our understanding of LRP6 structure and function has relied on studies involving its overexpression, and regulation of the endogenous receptor by the Wnt ligand has remained unexplored. Using a highly sensitive and specific antibody to LRP6, we demonstrate that the endogenous receptor is modified by N-glycosylation and is phosphorylated in response to Wnt stimulation in a sustained yet ligand-dependent manner. Moreover, following triggering by Wnt, endogenous LRP6 is internalized and recycled back to the cellular membrane within hours of the initial stimulus. Finally, we have identified a novel feedback mechanism by which Wnt, acting through β-catenin, negatively regulates LRP6 at the mRNA level. Together, these findings contribute significantly to our understanding of LRP6 function and uncover a new level of regulation of Wnt signaling. In light of the direct role that the Wnt pathway plays in human bone diseases and malignancies, our findings may support the development of novel therapeutic approaches that target Wnt signaling through LRP6.

scholarly journals Estrogen-related receptor α regulates osteoblast differentiation via Wnt/β-catenin signaling

2012 ◽  
Vol 48 (2) ◽  
pp. 177-191 ◽  
Author(s):  
Kathryn L Auld ◽  
Stephen P Berasi ◽  
Yan Liu ◽  
Michael Cain ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Osteoblast Differentiation ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Wnt Signaling Pathway ◽  
Bone Diseases ◽  
Luciferase Reporter ◽  
Orphan Nuclear Receptor ◽  
Estrogen Related Receptor

Based on its homology to the estrogen receptor and its roles in osteoblast and chondrocyte differentiation, the orphan nuclear receptor estrogen-related receptor α (ERRα (ESRRA)) is an intriguing therapeutic target for osteoporosis and other bone diseases. The objective of this study was to better characterize the molecular mechanisms by which ERRα modulates osteoblastogenesis. Experiments from multiple systems demonstrated that ERRα modulates Wnt signaling, a crucial pathway for proper regulation of bone development. This was validated using a Wnt-luciferase reporter, where ERRα showed co-activator-dependent (peroxisome proliferator-activated receptor gamma co-activator 1α, PGC-1α) stimulatory effects. Interestingly, knockdown of ERRα expression also enhanced WNT signaling. In combination, these data indicated that ERRα could serve to either activate or repress Wnt signaling depending on the presence or absence of its co-activator PGC-1α. The observed Wnt pathway modulation was cell intrinsic and did not alter β-catenin nuclear translocation but was dependent on DNA binding of ERRα. We also found that expression of active ERRα correlated with Wnt pathway effects on osteoblastic differentiation in two cell types, consistent with a role for ERRα in modulating the Wnt pathway. In conclusion, this work identifies ERRα, in conjunction with co-activators such as PGC-1α, as a new regulator of the Wnt-signaling pathway during osteoblast differentiation, through a cell-intrinsic mechanism not affecting β-catenin nuclear translocation.

scholarly journals Wnt signaling in bone formation and its therapeutic potential for bone diseases

2013 ◽  
Vol 5 (1) ◽  
pp. 13-31 ◽  
Author(s):  
Jeong Hwan Kim ◽  
Xing Liu ◽  
Jinhua Wang ◽  
Xiang Chen ◽  
Hongyu Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Wnt Signaling ◽  
Therapeutic Potential ◽  
Bone Diseases

Wnt signaling in osteoblasts and bone diseases

Gene ◽  
2004 ◽  
Vol 341 ◽  
pp. 19-39 ◽  
Author(s):  
Jennifer J. Westendorf ◽  
Rachel A. Kahler ◽  
Tania M. Schroeder
Keyword(s):  
Wnt Signaling ◽  
Bone Diseases

scholarly journals Wnt signaling as a therapeutic target for bone diseases

2009 ◽  
Vol 13 (4) ◽  
pp. 485-496 ◽  
Author(s):  
Luke H Hoeppner ◽  
Frank J Secreto ◽  
Jennifer J Westendorf
Keyword(s):  
Wnt Signaling ◽  
Therapeutic Target ◽  
Bone Diseases

Wnt signaling pathway regulates the differentiation of hepatic progenitor cells

2010 ◽  
Vol 34 (8) ◽  
pp. S41-S41
Author(s):  
Yang Bi ◽  
Yun He ◽  
Tingyu Li ◽  
Tao Feng ◽  
Tongchuan He
Keyword(s):  
Wnt Signaling ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Hepatic Progenitor Cells

417: The Human Androgen Receptor Gene is a Primary Target of the WNT Signaling Pathway

2006 ◽  
Vol 175 (4S) ◽  
pp. 136-136
Author(s):  
Ralph Buttyan ◽  
Xuezhen Yang ◽  
Min-Wei Chen ◽  
Debra L. Bemis ◽  
Mitchell C. Benson ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Receptor Gene ◽  
Wnt Signaling Pathway ◽  
Androgen Receptor Gene ◽  
Primary Target ◽  
Human Androgen Receptor Gene ◽  
Human Androgen Receptor
Sign in / Sign up

Export Citation Format

Share Document