Wnt signaling as a therapeutic target for bone diseases.
BACKGROUND
There is a need to develop new bone anabolic agents because current bone regeneration regimens have limitations. The Wingless-type MMTV integration site (Wnt) pathway has emerged as a regulator of bone formation and regeneration.


OBJECTIVE
To review the molecular basis for Wnt pathway modulation and discuss strategies that target it and improve bone mass.


METHODS
Data in peer-reviewed reports and meeting abstracts are discussed.


CONCLUSIONS
Neutralizing inhibitors of Wnt signaling have emerged as promising strategies. Small-molecule inhibitors of glycogen synthase kinase 3beta increase bone mass, lower adiposity and reduce fracture risk. Neutralizing antibodies to Dickkopf 1, secreted Frizzled-related protein 1 and sclerostin produce similar outcomes in animal models. These drugs are exciting breakthroughs but are not without risks. The challenges include tissue-specific targeting and consequently, long-term safety.
Hoeppner
Luke H
LH
Graduate Program in Microbiology, Immunology and Cancer Biology, University of Minnesota, Minneapolis, MN, USA.
Secreto
Frank J
FJ
Westendorf
Jennifer J
JJ