Front Matter

Chapter 3 Musculoskeletal Structure and Physiology 45

XIV, XVI, XIX, XX, XXI, and XXII), filamentous
collagens (type VI), short‐chain collagens (types
VIII and X), and basement membrane collagens
(types IV, VII, XV, and XVIII). Nonfibrillar col­
lagens do not assemble into discrete fibrils;
however, many associate with fibrillar colla­
gens and regulate fibril assembly, fibril diame­
ter, and interfibrillar interactions (FACIT
collagens) (Kadler et  al., 1996; Zhang et  al.,
2005). Others contribute to the unique mechani­
cal properties of specific tissues (filamentous
and basement membrane collagens).
Biosynthesis of collagen involves transcrip­
tion and translation of the alpha chain gene,
and  production of a pre‐pro‐collagen peptide.
During translation, specific proline and lysine
residues within this molecule are hydroxylated
by ascorbic acid‐ and iron‐dependent prolyl‐
and lysyl‐hydroxylases. Hydroxylated pre‐pro‐
alpha chains undergo intracellular self‐assembly
into triple helical procollagen. The globular
amino‐ and carboxy‐termini of the procollagen
molecules are subsequently cleaved by various
metalloproteinases resulting in the formation of
tropocollagen. Tropocollagen molecules are
secreted from the cell where they assemble into
a variety of higher order structures according to
specific tissue requirements. Extracellular tro­
pocollagen molecules are further stabilized by
intermolecular crosslinks as well as noncovalent
association with other ECM components.

Within the ECM, fibrillar tropocollagen

molecules further assemble in a staggered fash­

ion into nascent fibrils. These fibrils are stabi­

lized by intermolecular crosslinks catalyzed by

lysyl‐oxidase enzymes. Numerous nonfibrillar

collagens, other proteins, proteoglycans, and

proteolipids associate closely with the surfaces

of collagen fibrils and regulate interfibrillar

cohesion and interactions (Chapman, 1989).

Groups of fibrils are further organized in

hierarchical fashion into fibers, which are them­

selves further bundled into fascicles (Figure 3.1).

Collagen fibers are the basic macroscopic

structural units of many musculoskeletal

structures such as tendons and ligaments.

Elastin

Elastin is an important component of many

musculoskeletal tissues, including tendons,

ligaments, myofascial structures, joint capsule,

and articular cartilage. Elastin provides tissues

with elasticity, which refers to the ability of a

tissue to undergo reversible deformation.

The  content of elastin within musculoskeletal

tissues varies greatly depending on the

requirement for elasticity. Elastin is a minor

component of bone, where it occurs

predominantly with the walls of blood vessels;

however, it is particularly abundant within the

ECM of structures that undergo repeated cycles

Tropocollagen

Microfibril

Fibril

Fiber

Fascicle

Tendon/Ligament

Figure 3.1 Schematic depiction of the hierarchical structuring of collagen fibers in tendons and ligaments.