Biomedical Engineering Reference
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Figure 1. Diagram of growth plate.
osteoblast progenitors will differentiate into mature osteoblasts that secrete a specific bone
ECM that will replace the cartilaginous ECM. At both ends of a bone, chondrocytes become
restricted to a narrow zone forming the growth plate, which is responsible for longitudinal
bone growth.
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A typical growth plate contains resting, proliferating, prehypertrophic, and hy-
pertrophic chondrocytes (Fig. 1).
Beyond embryonic development and throughout adult life, bone undergoes continual re-
sorption and formation through a dynamic process called bone remodeling. Bone remodeling
starts when osteoclasts resorb mineralized ECM that is then replaced by a new bone ECM
secreted by osteoblasts.
Transcription Control of Chondrocyte Differentiation
Beyond their morphological differences, various chondrocyte subpopulations express spe-
cific molecular markers.
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These various molecular markers help also to define each specific
subpopulation. In the reserve zone, cells are small and resting. In the adjacent proliferative
zone, however, cells are rapidly dividing to increase their numbers which contributes to the
ongoing growth of bone. Both resting and proliferating chondrocytes express
α
1(II) collagen.
Cells in the prehypertrophic zone express
α
1(II) collagen albeit at a lower level, Indian hedge-
hog, and PPR, a gene encoding the receptor for both parathyroid hormone (PTH) and
PTH-related peptide (PTHrP). Finally, chondrocytes of the hypertrophic zone express
α
1(X)
collagen but not anymore
α
1(II) collagen.
The earliest molecule required for specifying a cell fate during skeletogenesis identified to
date is Sox9, a high-mobility-group (HMG) domain containing transcription factor. It was
shown that Sox9 is the gene inactivated in campomelic dysplasia patients, a disease character-
ized by skeletal malformation and XY sex reversal.
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In mouse embryo, Sox9 is expressed
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