TY - JOUR
T1 - Update on Wnt signaling in bone cell biology and bone disease
AU - Monroe, David G.
AU - McGee-Lawrence, Meghan E.
AU - Oursler, Merry Jo
AU - Westendorf, Jennifer J.
N1 - Funding Information:
The authors are supported by several NIH grants ( AG04875, AR48147, AR60140, DE020194, DK91145 ).
PY - 2012/1/15
Y1 - 2012/1/15
N2 - For more than a decade, Wnt signaling pathways have been the focus of intense research activity in bone biology laboratories because of their importance in skeletal development, bone mass maintenance, and therapeutic potential for regenerative medicine. It is evident that even subtle alterations in the intensity, amplitude, location, and duration of Wnt signaling pathways affects skeletal development, as well as bone remodeling, regeneration, and repair during a lifespan. Here we review recent advances and discrepancies in how Wnt/Lrp5 signaling regulates osteoblasts and osteocytes, introduce new players in Wnt signaling pathways that have important roles in bone development, discuss emerging areas such as the role of Wnt signaling in osteoclastogenesis, and summarize progress made in translating basic studies to clinical therapeutics and diagnostics centered around inhibiting Wnt pathway antagonists, such as sclerostin, Dkk1 and Sfrp1. Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease.
AB - For more than a decade, Wnt signaling pathways have been the focus of intense research activity in bone biology laboratories because of their importance in skeletal development, bone mass maintenance, and therapeutic potential for regenerative medicine. It is evident that even subtle alterations in the intensity, amplitude, location, and duration of Wnt signaling pathways affects skeletal development, as well as bone remodeling, regeneration, and repair during a lifespan. Here we review recent advances and discrepancies in how Wnt/Lrp5 signaling regulates osteoblasts and osteocytes, introduce new players in Wnt signaling pathways that have important roles in bone development, discuss emerging areas such as the role of Wnt signaling in osteoclastogenesis, and summarize progress made in translating basic studies to clinical therapeutics and diagnostics centered around inhibiting Wnt pathway antagonists, such as sclerostin, Dkk1 and Sfrp1. Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease.
KW - Bone mineral density
KW - Lrp5
KW - Lrp6
KW - Polymorphisms
KW - R-spondin
KW - Sclerostin
KW - β-catenin
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U2 - 10.1016/j.gene.2011.10.044
DO - 10.1016/j.gene.2011.10.044
M3 - Review article
C2 - 22079544
AN - SCOPUS:84155188831
SN - 0378-1119
VL - 492
SP - 1
EP - 18
JO - Gene
JF - Gene
IS - 1
ER -