Front Matter

44 Canine Sports Medicine and Rehabilitation

mechanical properties and functionality of a
given tissue. These properties vary greatly
amongst tissues, reflecting the diverse functional
roles to which different structures are adapted.

Cellular components of musculoskeletal
tissues

Musculoskeletal tissues contain a variety of
cell types. The tissue‐specific cells within mus­
culoskeletal structures are named in accordance
with the tissues they inhabit (tenocytes within
tendon, chondrocytes within cartilage, etc.).
The majority of these are fully differentiated
cells that are responsible for the synthesis and
lifelong turnover of the ECM that surrounds
them. All connective tissues also contain small
numbers of progenitor cells that represent
variable stages of lineage commitment from
multipotent mesenchymal stem cells to tissue‐
specific blast forms (osteoblasts, tenoblasts,
etc.). Progenitor cells play important roles in
repair, regeneration, and adaptive remodeling
of connective tissues.
With the exception of articular chondrocytes,
musculoskeletal tissue cells are highly inter­
connected through adherens and gap junctions
(Chi et al., 2005; Civitelli, 2008). These intercon­
nections are established during development
and allow close intercellular communication.
The broad connectivity of the cellular network
enhances the ability of tissues to mount
regional responses to specific biological or
mechanical stimuli (Ko & McCulloch, 2001;
Wall & Banes, 2005). Connective tissue cells are
also highly  responsive to mechanical stimuli.
Mechanotransduction is the process by which
cells mount biological responses to mechanical
stimuli (Ramage et  al., 2009). The mechanical
stresses imposed upon musculoskeletal tissues
are borne primarily by the ECM. The resulting
strains within the ECM may trigger cellular
responses through a variety of mechanisms,
including direct deformation of the plasma
membrane and alteration of transmembrane
ion conductance, deflection of the primary
cilium, activation of cell‐surface receptors
by  extracellular fluid shears, or ligand‐
independent activation of signaling receptors
(Silver & Siperko, 2003; Bonewald, 2006).
The  response of  a tissue to a mechanical

stimulus may be either physiological or patho­

logical, depending on the state of the tissue

and the nature of the stimulus. Physiological

responses result in appropriate adaptive

changes of the ECM that enhance a tissue’s

ability to meet the demands placed upon it.

An  example of adaptive remodeling is the

hypertrophy and mitochondrial biogenesis

that occurs within skeletal muscle in response

to athletic conditioning.

Molecular components of extracellular

matrix

Collagen

Collagen is the most abundant protein in the

body, and is a ubiquitous component of all con­

nective tissues. All collagens are triple helical

proteins made up of three individual polypep­

tides called alpha chains. Homotypic collagens

are composed of three identical alpha chains.

Heterotypic collagens are composed of various

combinations of alpha chains that differ in

amino acid sequence. In mammals, there are 34

known alpha chain genes and at least 28 distinct

collagen types. Use of alternative transcription

start sites as well as alternative splicing of indi­

vidual alpha chain transcripts results in a wide

variety of collagen configurations with diverse

structures and unique mechanical properties

(Hulmes, 2002).

Collagens may be divided into several major

groups: The fibrillar collagens are of primary

importance in the musculoskeletal system as

they are the major structural components of

connective tissues such as tendon, ligament,

cartilage, and bone. The major fibrillar colla­

gens are types I, II, and III. Type I collagen

forms  linear and extensively crosslinked mac­

romolecular structures that impart high tensile

strength to tendons and ligaments. It is also the

most abundant collagen type in bone. Type II

collagen is the predominant collagen in hyaline

cartilage. Within articular cartilage, type II

collagen fibrils are crosslinked into extensive

three‐dimensional networks that provide resist­

ance to deformation in a multitude of direc­

tions. Other collagen groups include the

fibril‐associated collagens with interrupted

triple helices (FACIT collagens, types IX, XII,