C h a p t e r 4 2
Structure and Function of the Skeletal System
1071
Bone Formation.
After osteo-
clastic activity has ceased, osteo-
blasts begin to deposit the organic
matrix (osteoid) on the wall of the
osteon canal. As successive lamel-
lae of bone are deposited, the canal
ultimately attains the relative pro-
portions of the original osteon. In
the formation and maintenance of
bone, osteoblasts provide much of
the local control because not only
do they produce new bone matrix,
they play an essential role in mediat-
ing osteoclast activity. Many of the
primary stimulators of bone resorp-
tion, such as parathyroid hormone,
have minimal or no direct effects
on osteoclasts. Once the osteoblast,
which has receptors for these sub-
stances, receives the appropriate
signal, it releases a soluble mediator
called
RANKL
that induces osteo-
clast activity.
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New osteon
Osteoblasts
Osteoblasts
Osteoclasts
Osteoid
Osteoid
OPG
RANKL
RANK receptor
Differentiation
Bone
Osteoblast/stromal
precursor cell
Osteoclast
precursor cell
Activated osteoclast
Control of Bone Metabolism
and Remodeling.
The pivotal
pathway linking osteoclast-mediated
bone resorption with osteoblast-
mediated bone formation consists
of a paracrine system that includes
RANKL, its receptor RANK, and
a soluble protein called
osteopro-
tegerin
(OPG). RANKL, which
is produced by osteoblasts and
their precursors, binds to RANK,
promoting osteoclast differentia-
tion and proliferation. The soluble
OPG molecule, which is produced
by a number of tissues, acts as a
decoy receptor to block the action
of RANKL. This system ensures
the tight coupling of bone forma-
tion and resorption, and provides
a means whereby a wide variety of
biologic mediators (e.g., hormones,
cytokines, growth factors) influence
the homeostasis of bone.
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