Selective targeting of RANK signaling pathways as new therapeutic strategies for osteoporosis.
BACKGROUND
Osteoporosis has become a worldwide health and social issue due to an aging population. Four major antiresorptive drugs (agents capable of inhibiting osteoclast formation and/or function) are currently available on the market: estrogen, selective estrogen receptor modulators (SERMs), bisphosphonates and calcitonin. These drugs either lack satisfactory efficacy or have potential to cause serious side effects. Thus, development of more efficacious and safer drugs is warranted.


METHODS
The discovery of the receptor activator of NF-kappaB ligand (RANKL) and its two receptors, RANK and osteoprotegerin (OPG), has not only established a crucial role for the RANKL/RANK/OPG axis in osteoclast biology but also created a great opportunity to develop new drugs targeting this system for osteoporosis therapy. This review focuses on discussion of therapeutic targeting of RANK signaling.


RESULTS
An update on the functions of RANKL and an overview of the known RANK signaling pathways in osteoclasts. A discussion of rationales for exploring RANK signaling pathways as potent and specific therapeutic targets to promote future development of better drugs for osteoporosis.


CONCLUSIONS
Several RANK signaling components have the potential to serve as potent and specific therapeutic targets for osteoporosis.
Jules
Joel
J
University of Alabama at Birmingham, Department of Pathology, 35294, USA.
Ashley
Jason W
JW
Feng
Xu
X
D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D053244:Osteoprotegerin; D053245:RANK Ligand