Bone and Cartilage – its Structure and Physical Properties - Biomechanics of Hard Tissues - page 42

and pathologic states. The role of the RANKL/RANK system is important not only
in bone but also in other tissues.
OPG is a RANK homolog, and works by binding to RANKL on the os-
teoblast/stromal cells, thus blocking the RANKL- RANK ligand interaction between
osteoblast/stromal cells and osteoclast precursors. This has the effect of inhibiting
the differentiation of the osteoclast precursor into a mature osteoclast. Recombi-
nant human OPG acts on the bone, increasing bone mineral density and bone
volume [176-181]. OPG can bind to RANKL and prevent its interaction with RANK
to inhibit osteoclast formation, but its effects on other cellular functions of RANKL
have yet to be determined.
Discovery of the RANK signaling pathway in the osteoclast has provided insight
into the mechanisms of osteoclastogenesis and activation of bone resorption, and
how hormonal signals impact bone structure and mass. Further study of this
pathway has provided the molecular basis for developing therapeutics to treat
osteoporosis and other diseases of bone loss [180].
Osteoclast formation requires the presence of RANK osteoblasts (RANK) and
macrophage colony-stimulating factor (M-CSF). These membrane-bound proteins
are produced by neighboring stromal cells and osteoblasts. Thus, a direct contact
between these cells and osteoclast precursors is required [168, 169, 178-183].
1.3.5.3 TACE
Tumor necrosis factor-alpha converting enzyme (TACE) is a kind of metalloprotease
disintegrins, also known as ADAM17 . It is a modular transmembrane protein with
a zinc-dependent catalytic domain. TACE can cleave or shed the ectodomain of
several membrane-bound proteins. In particular, TACE can shed several cytokines
from the cell membrane, including RANKL [184, 185].
1.3.5.4 Bone Modeling and Remodeling
Bone modeling develops during the organism's youth and deals with the bone
growth in length and width. In this process, a new bone is added (a subprocess
called ossification or bone formation ) to a side of the periosteal surface, and the old
bone is removed from the skeleton (a subprocess called bone resorption )ontheside
of the endosteal surface. The modeling differs from remodeling in that processes
of bone formation and bone resorption are realized at different surfaces of the bone
Figure 1.26.
A bone is constantly renewed. The old bone is removed and the new bone is laid
down. This process is called bone remodeling . Thus, bone remodeling is a lifelong
process, where an old bone is removed from the skeleton and a new bone is added.
These processes control not only the reshaping or replacement of bone during
growth and following injuries like fractures but also microdamage, which occurs
during normal activity. Remodeling responds also to functional demands of the
mechanical loading. As a result bone is added where needed and removed where it
is not required.
In the first year of life, almost 100% of the skeleton is replaced. In adult compact
bone, remodeling proceeds at about 10% per year, and in spongy bone, it proceeds