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Vol. 14, Issue 1, 173-189, January 2003
*Department of Oral/Craniofacial Biological Sciences,
University of Maryland, Baltimore, Maryland 21201; Departments of
Osteopontin (OPN) was expressed in murine wild-type osteoclasts,
localized to the basolateral, clear zone, and ruffled border membranes,
and deposited in the resorption pits during bone resorption. The lack
of OPN secretion into the resorption bay of avian osteoclasts may be a
component of their functional resorption deficiency in vitro.
Osteoclasts deficient in OPN were hypomotile and exhibited decreased
capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be
required for osteoclast motility and bone resorption. Exogenous addition of OPN to OPNPediatrics and §Bone and
Mineral Divisions, Department of Medicine, Washington University School
of Medicine, St. Louis, Missouri 63110; and
¶Department of Cell Biology and Neuroscience,
Rutgers University, Nelson Labs, Piscataway, New Jersey 08854-8000
/ osteoclasts increased the surface
expression of CD44, and it rescued osteoclast motility due to
activation of the 
v
3 integrin.
Exogenous OPN only partially restored bone resorption because addition
of OPN failed to produce OPN secretion into resorption bays as seen in
wild-type osteoclasts. As expected with these in vitro findings of
osteoclast dysfunction, a bone phenotype, heretofore unappreciated, was
characterized in OPN-deficient mice. Delayed bone resorption in
metaphyseal trabeculae and diminished eroded perimeters despite an
increase in osteoclast number were observed in histomorphometric
measurements of tibiae isolated from OPN-deficient mice. The
histomorphometric findings correlated with an increase in bone rigidity
and moment of inertia revealed by load-to-failure testing of femurs.
These findings demonstrate the role of OPN in osteoclast function and
the requirement for OPN as an osteoclast autocrine factor during bone remodeling.
Corresponding author. E-mail address:
mac001{at}dental.umaryland.edu.
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