50 Etiopathogenesis of Cruciate Ligament Rupture
facilitate direct communication, variation in cell
morphology between breeds with a different
risk of CrCL rupture may reflect differences in
cruciate ligament physiology.
The canine CrCL undergoes a partial fibro-
cartilagenous transformation as described in
human ACL, which may represent chronic
and irreversible degeneration. This idiopathic
degeneration is a common histologic finding of
intact CrCL, despite its grossly normal appear-
ance. A histologic study reported that the CrCL
of dogs weighing greater than 15 kg consis-
tently had microscopic evidence of degenera-
tive changes by 5 years of age (Vasseuret al.
1985). These changes are characterized by a loss
of ligament fibroblasts, metaplasia of surviving
fibroblasts to chondrocytes, and failure to main-
tain collagen fiber bundles, which progressed
in severity with age. The CrCL in dogs weigh-
ing less than 15 kg generally had less severe
alterations than those in heavier dogs, and the
onset of the degenerative process was delayed
by several years. The deep core region of the
CrCL deteriorates earlier than the superficial
epiligamentous region, and the mid-portion of
the CrCL deteriorates earlier than regions close
to bony attachments.
In ruptured CrCL, more severe changes such
as hyalinization, mineralization, and cloning
of chondrocyte-like cells can also occur. How-
ever, inflammatory or reparative responses are
rarely observed (Hayashiet al. 2003a). Signifi-
cant loss of fibroblasts from the core region of
ruptured CrCL occurs. In contrast, cell num-
ber densities are similar in ruptured and intact
CrCL in the epiligamentous region (Hayashi
et al. 2003a,b). In ruptured CrCL, the num-
bers of typical ligament fibroblasts (fusiform
and ovoid cells) are decreased, while num-
bers of cells exhibiting chondroid transforma-
tion (spheroid cells) are increased in the core
region (Figures 6.1–6.3). The structure of the
ECM collagen in the core region is extensively
disrupted in ruptured CrCL. Rupture of the
CrCL is also associated with disruption of the
hierarchical architecture of ECM collagen, with
a loss of the normal crimp and loss of bire-
fringence (Figures 6.1, 6.2, and 6.4). A histolog-
ical study reported that crimp was no longer
detectable in many ligament specimens from
dogs with CrCL rupture (Figures 6.1, 6.4, and
6.5) (Hayashiet al. 2003a). Interestingly, in the
(B)50 μm50 μm(A)Figure 6.2 Photomicrographs of longitudinal frozen
sections of intact cranial cruciate ligament (CrCL) from a
2-year-old ovariohysterectomized Beagle (A) and an
8-year-old ovariohysterectomized Labrador Retriever (B)
obtained via bright-light microscopy. Specimens were
stained histochemically for lactate dehydrogenase (LDH),
a marker of cell viability. (A) Central part of the core
region of the intact CrCL from a young dog. Notice
parallel rows of fusiform and ovoid LDH-stained ligament
fibroblasts, with an organized extracellular matrix (ECM)
containing crimped collagen fibers. (B) Central part of the
core region of the intact CCL from an old dog. Note the
decreased number of ligament fibroblasts; many cells are
devitalized (low LDH) with an ovoid phenotype.
Collagen fibers within the ECM have also been
disrupted.ruptured CrCL specimens in which crimp was
still detectable, crimp length was significantly
increased, and the crimp angle tended to be
lower compared with intact CrCL from young
dogs (Figure 6.5) (Hayashiet al. 2003a). These
data suggest that the remaining organized colla-
gen experiences mechanical overload that elon-
gates the crimp within the collagen fibers, as
progressive CrCL rupture develops over time,