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Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation
D.L Lacey ,
E Timms ,
H.-L Tan ,
M.J Kelley ,
C.R Dunstan ,
T Burgess ,
R Elliott ,
A Colombero ,
G Elliott ,
S Scully ,
H Hsu ,
J Sullivan ,
N Hawkins ,
E Davy ,
C Capparelli ,
A Eli ,
Y.-X Qian ,
S Kaufman ,
I Sarosi ,
V Shalhoub ,
G Senaldi ,
J Guo ,
J Delaney ,
W.J Boyle
April 1998
April 1998
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Abstract
The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine
that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in
the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique
hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates
the rapid induction of genes that typify osteoclast development. OPGL directly activates
isolated mature osteoclasts in vitro, and short-term administration into normal adult
mice results in osteoclast activation associated with systemic hypercalcemia. These
data suggest that OPGL is an osteoclast differentiation and activation factor. The
effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and
OPG are key extracellular regulators of osteoclast development.