Identification of important interactions between subchondral bone ...

CHAPTER 2: Introduction
number of active chondrocytes occurs with age along with a reduction in their response to
anabolic factors. Therefore, the increased loss of chondrocytes during the later stages of life and
thus the increasing lack of regeneration eventually result in damaged cartilage and the
development of OA 66,67,68,69,70 . However, in the pathogenesis of OA, chondrocytes proliferate to
form multiple cells within a chondron, which is a pivotal change from normal cartilage, where
more than 2–3 cells are unusual, even in the elderly 71 . These clusters of chondrocytes in OA are
not to be mistaken for the chondrocytes in healthy adult cartilage, as chondrocytes can change
into different phenotypes during the progression of OA:
An anabolic phenotype that expresses ECM proteins; e.g. collagen type II and aggrecan 72
A catabolic phenotype that expresses proteolytic enzymes that degrade the ECM 11,73,74
A Hypertrophic phenotype that expresses collagen type X before it undergoes apoptosis 75
A dedifferentiated phenotype that expresses collagen type I (often in repair areas after damage 76,77
A chondroblastic phenotype that expresses fetal type IIA collagen and type III collagen 78
The differentiation of chondrocytes into these phenotypes probably occurs due to a “panic-
attack” from the insufficient adult chondrocytes, who cannot keep up with the repair
mechanisms of damaged cartilage. As a solution, the very productive phenotypes seen from the
skeletal development are starting to emerge. Evidence of phenotypic change for chondrocytes is
reflected in the presence of collagens not normally found in adult articular cartilage. As an
example, the splice-variant of collagen type II, type IIA (which is normally expressed by
chondroblasts during development) is re-expressed in early and late-stage OA 78 . Other indicators
of a potential reversion of the cells to an earlier developmental phenotype are the hypertrophic
chondrocyte marker, collagen type X 79 as well as the general increased production of proteins,
proteinases, growth factors, cytokines, and other inflammatory mediators by more
active/productive chondrocytes 80,81,82 .
The adult articular chondrocytes normally maintain the cartilage
homeostasis with a low turnover of matrix constituents. In OA,
the chondrocytes attempt to recapitulate phenotypes of early stages
of cartilage development, whose rate of synthesis of matrix
constituents are faster. However, and unfortunately, the original
cartilage cannot be replicated.
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