Biomedical Engineering Reference
In-Depth Information
presence of M-CSF and RANKL, a tumor necrosis factor family member [36].
RANKL interacts with a receptor on an osteoclast precursor called RANK.
Further differentiation of the immature osteoclast into mature and active
osteoclasts occurs only under the continued presence of RANKL [37]. The
RANK-RANKL interaction results in activation, differentiation, and fusion
of hematopoietic cells of the osteoclast lineage so that they begin the pro-
cess of resorption. Further, it prolongs osteoclast survival by suppressing
apoptosis [38].
Osteoblast development follows a different course, beginning with the
local proliferation of mesenchymal stem cells residing in the marrow, which
can also give rise to other types of cells such as myocytes, chondrocytes,
and adipocytes [39]. Proliferating precursors are pushed toward the
preosteoblasts—responding osteoblasts (ROBs)—under the complex effects
of specific factors such as PTH and TGF-β [39]. After further differentiation,
ROBs mature to active osteoblasts (AOBs), which are responsible for bone
formation. Eventually, osteoblasts die or transform to either lining cells or
osteocytes [40].
The logical structure of the model is presented in Figure 6.1, which shows
the simplified lineages of osteoblasts, osteoclasts, and their interactions. See
references 2 and 3 for more details of this model.
Haematopoetic
stem cell
Mesenchymal
stem cell
TGF- β(+)
M-CSF
OPG(-)
Preosteoblast
Preosteoclast
TGF- β(-)
M-CSF
Mature
osteoblast
Immature
osteoclast
PTH(-)
Osteocyte, lining
cell apoptotic
osteoblast
RANK(+)
Mature
osteoclast
TGF- β(+)
Apoptotic
osteoclast
RANK(-)
FIGURE 6.1
Schematic representation of structure of the model. The solid arrow with a (+) or (-) beside it
represents a stimulatory or inhibitory action by the factor. The thin frame squares indicate
types of cells that are included in this model.
