Biomedical Engineering Reference
In-Depth Information
2.4.1 Bone growth
Bones are formed through two distinct developmental processes—
intramembranous and endochondral bone formation. Intramembranous bone
formation
gives rise to the flat bones that comprise the cranium and medial
clavicles, and begins with the condensation of mesenchymal cells which
differentiate into osteoblasts and develop ossification centers by direct bone
matrix deposition. This forms plates which expand during development, but
do not fuse at their
junctions with other cranial bones.
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These junctions
or sutures maintain separation
between membranous bones and regulate
expansive growth
of the skull.
endochondral bone formation gives rise to long bones
that comprise the
appendicular skeleton, facial bones, vertebrae
and portions of the clavicles.
as with intramembranous bone formation, endochondral bone formation
also begins with the condensation of mesenchymal cells; however, during
endochondral bone formation, the differentiation of these cells gives rise to
a proliferating
population of centrally localized type II collagen-expressing
chondrocytes and more peripherally localized type I collagen-expressing
perichondrial cells.
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The chondrocytes
produce a specialized extracellular
matrix containing
type II collagen which forms a cartilaginous template
(or 'anlage'). Midway between the ends of this elongated template,
chondrocytes exit the cell cycle (hypertrophy) and an ossification center
forms by neovascularization of the initially avascular
cartilaginous template.
Osteoblasts that are associated with the newly developed vasculature begin
secretion and mineralization of a
type I collagen-containing extracellular
matrix.
As bones grow, this center of ossification propagates toward the
two
epiphyseal
plates.
The epiphyseal growth plates allow longitudinal bone growth by a sequence
of chondrocyte proliferation, differentiation to hypertrophy and cell death
(apoptosis) (Fig. 2.7). Proximally (toward
the end of a developing bone), a
pool of chondrocytes (called
the resting or reserve zone) supplies cells to a
population of
proliferating chondrocytes. Proliferating chondrocytes in turn
differentiate to form a transient pool of prehypertrophic and
then a more long-
lived pool of hypertrophic chondrocytes. at the
distal end of the epiphyseal
growth plate, hypertrophic chondrocytes
die by apoptosis and are replaced
by trabecular bone. In this
manner, hypertrophic chondrocytes provide a
template for the formation
of trabecular
bone. chondrocyte proliferation in
this process is stopped by the negative influence of local fibroblast growth
factor (FGF) signaling,
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whereas the cytokine parathyroid hormone-related
peptide (PThrP) functions to stop chondrocyte differentiation to hypertrophy
by signaling through its receptor.
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The determination of whether mesenchymal cells differentiate into either
bone-forming osteoblasts for intramembranous bone formation or cartilage
producing chondrocytes for endochondral bone formation is regulated
