8

Cruciate Ligament Matrix

Metabolism and Development

of Laxity

Eithne Comerford

Introduction

Cruciate ligaments are comprised of cells and
extracellular matrix (ECM). Most skeletal lig-
aments contain approximately 60–80% water,
while nearly 70–80% of the dry weight of liga-
ment is collagen (Franket al. 1985). Up to 90%
of the ligamentous collagens is type I collagen,
the principle tensile-resistant fiber, but smaller
quantities of types III, V, and VI are also present
(Waggettet al. 1996). Smaller proportions of
matrix are composed of elastin, proteoglycans
and other biochemical substances such as DNA
from cells, enzymes, glycoproteins, lipoproteins
and integrins (Franket al. 1985; Amielet al. 1995;
Smithet al. 2014; Kharazet al. 2016; Ruschkeet al.
2016).
The majority of cells in ligaments are fibrob-
lasts (sometimes referred to as ligamentocytes)
(Vasseuret al. 1985), although fibrocartilage
cells are present at attachment sites. The fibrob-
lasts have multiple small cellular processes or
microvilli which may alter in cruciate ligaments
from dog breeds with differing risk of cruciate
ligament rupture (CR) (Smithet al. 2012) (Fig-
ure 8.1). The cells are linked both within the
same row and in adjacent rows by connexins,

allowing a three-dimensional communicating

network that extends throughout the ligament

(Benjamin & Ralphs 1998).

The mechanical properties of cruciate liga-

ments are dependent on the composition and

structure of the ECM, in particular collagen.

Collagen turnover is a balance between its

synthesis and degradation (Cawston 1998). To

date, most interest in cruciate ligament ECM

metabolism has centered on degradation (Com-

erfordet al. 2005; Hasegawaet al. 2013; Naka-

haraet al. 2013). However, some research has

been conducted into the synthesis of ECM com-

ponents (e.g., collagen) in ligament, by mea-

suring terminal propeptide levels (Slusset al.

2001; Quasnichkaet al. 2005), but this has yet to

be evaluated in the canine cranial cruciate lig-

ament (CrCL). The synthesis of ECM compo-

nents after mechanical load has been evaluated

in canine CrCL cells (Breshearset al. 2010a).

Proteases, such as the cathepsins (Muiret al.

2002; Barrettet al. 2005; Muiret al. 2005a,b)

and matrix metalloproteinases (MMPs; collage-

nases, stromelysins, and gelatinases) (Muiret al.

2005a,b; Comerfordet al. 2006; Breshearset al.

2010b) have been mainly implicated in ECM

degradation.

Advances in the Canine Cranial Cruciate Ligament, Second Edition. Edited by Peter Muir. © 2018 ACVS Foundation.
This Work is a co-publication between the American College of Veterinary Surgeons Foundation and Wiley-Blackwell.

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