Biomedical Engineering Reference
In-Depth Information
38.5 Vascularization and its Absence in Cartilage
Like most tissues of the body bone is a well-vascularized tis-
sue. Cartilage, however, is avascular, with no blood vessels cross-
ing the subchondral plate into the calcified cartilage layer. This
offers a unique set of considerations for tissue engineers. Maintain-
ing cartilage in an avascular state begins at development and is
a continuing process throughout life. The formation of bone from
a cartilage template via endochondral ossification (for review see
Ref. 25) and its vascularization without the formation of blood ves-
sels in the articular cartilage involves a delicate balance between
pro- and anti-angiogenic factor release from chondrocytes at dif-
ferent stages of development. The two most important factors in
this process are probably the anti-angiogenic factor chondromod-
ulin 1 and the pro-angiogenic factor vascular endothelial growth
factor (VEGF)-A. During development chondromodulin is heavily
expressed in proliferating chondrocytes, but when these begin to
hypertrophy its expression decreases with a concomitant increase
in VEGF expression.
26
This combination leads to blood vessel inva-
sion from the surrounding tissue, going hand in hand with matrix
mineralization and bone formation. Other factors have also been
identified as being critical for this process to take place, includ-
ing high-mobility group box 1 protein (HMGB1) and collagen type
X, both of which act as chemoattractants for blood vessels and
bone-formingcells.
27
,
28
Alongside chondromodulin, thrombospondin 1 and 2 and tissue
inhibitor of metalloproteinases (TIMP)-2 and 3 are also expressed
in developing cartilage but reduced in hypertrophic and calcified
zones.
26
,
29
,
30
Thepresenceofthesefactorsinmaturecartilageplays
an important role in preventing vessel invasion from the underly-
ing bone. VEGF-A plays a large role in the switch from vessel inhibi-
tion to invasion and is expressed in hypertrophic cartilage but not
in proliferating cartilage.
31
Several knockout studies have been per-
formed with regard to angiogenesis inhibitors (for review see Ref.
32). By expressing these various factors at different levels, a perfect
homeostasis is maintained between avascular hyaline cartilage and
the underlying vascularized bone tissue. Upsetting this balance may
beone cause ofthe onset ofOA.
33
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