Advances in the Canine Cranial Cruciate Ligament, 2nd edition

48 Etiopathogenesis of Cruciate Ligament Rupture

Histologic features of cruciate

ligament

The CrCLis a complex structure consisting of an
extracellular matrix (ECM) and a diverse popu-
lation of cells. It has distinctive histologic fea-
tures typical of dense collagenous connective
tissues (ligaments and tendons). The ECM pro-
teins in CrCL are primarily composed of type
I collagen. Bundles of collagen fibers are lon-
gitudinally oriented, mostly running parallel
to one another. Normal CrCL collagen fibers
have a recurrent undulating wave or crimped
structure (Figure 6.1) (Hayashi et al. 2003a).
The human ACL has been shown to also con-
tain collagen types III, IV, V and VI and other
ECM components, including glycosaminogly-

cans, fibronectin, laminin, entactin, tenascin,

and undulin (Neurath & Stofft 1992). The matrix

of the CrCLrepresents a complicated regulatory

network of proteins, glycoproteins, viscoelas-

tic fibers and glycosaminoglycans with multiple

functional interactions.

The predominant cell type in the CrCL

is the fibroblast. Ligament fibroblasts are

arranged in long parallel rows between colla-

gen fiber bundles. In the human ACL, three

different phenotypes of fibroblasts have been

described: fusiform or spindle-shaped, ovoid,

and spheroid (Murray & Spector 1999). The

cytoplasm of fusiform fibroblasts is intimately

attached to the extracellular collagen and

follows the crimped waveform of the fibers.

Ovoid and spheroid fibroblasts are situated in

Figure 6.1 Longitudinal sections of intact (A,B) and ruptured CrCL (C,D) from a 2-year-old ovariohysterectomized
Beagle and a 7-year-old castrated male Golden Retriever, respectively, viewed using bright-light (A,C) and circularly
polarized light (B,D) microscopy. (A,B) Intact CrCL from young dogs has a hierarchically organized structure.
Birefringence of the extracellular matrix (ECM) collagen and the crimped structure of collagen fiber bundles are clearly
visible in polarized light. (C,D) The disorganized regions of the ECM in ruptured CrCL exhibit a loss of birefringence and
crimp, as well as a loss of ligament fibroblasts. Scale bars= 100 μm. Source: Hayashiet al. 2003a. Reproduced with
permission from John Wiley & Sons, Inc.