The Role of Mechanobiology in the Attachment of Tendon to Bone - Structural Interfaces and Attachments in Biology - page 224

11.3 Mechanobiology in Musculoskeletal Tissue Homeostasis
and Development
A complex synergy between biophysical cues and biological processes gives rise
to the gradations in structure and composition observed at the tendon-to-bone
insertion. An improved understanding of the mechanotransduction mechanisms
by which the loading environment is linked to ECM production and ultimately to
tissue functional behavior will help guide the development of novel repair
strategies. Based primarily on mechanical cues, musculoskeletal tissues are con-
tinually remodeled throughout the lifespan. This enables tissues to heal after
injury and to adapt to environmental stimuli. The ability of musculoskeletal
tissues to remodel in response to the loading environment is critical, not only to
maintain mature tissue homeostasis, but also to direct the complex patterning
necessary for fetal and postnatal development.
Abnormal loading conditions that result from muscle paralysis, prolonged bed
rest, or overuse lead to pathological changes in the musculoskeletal system. Examples
of these conditions include repetitive loading-induced tendinopathies, unloading-
induced osteoporosis, joint instability-induced osteoarthritis, and paralysis-induced
developmental defects. For example, neonatal brachial plexus palsy often occurs
during difficult childbirth, resulting in paralysis and muscle imbalance in the shoulder
[ 35 , 36 ]. This paralysis leads to defects in glenohumeral joint development leading to
severe functional impairments [ 37 - 39 ].
11.3.1 Mechanobiology in Adult Musculoskeletal Tissue
Homeostasis
It is well established that musculoskeletal tissues are sensitive to changes in the
mechanical loading environment. This is apparent for all tissues (bone,
fibrocartilage, and tendon) and cell types (osteoblasts, chondrocytes, and
fibroblasts) at the tendon-to-bone insertion. Bone is in a constant state of
remodeling. Old bone is resorbed by osteoclasts and new bone is deposited by
osteoblasts. Control of the relative rates of bone formation and resorption
determines whether bone mass is maintained, gained, or lost. The idea that bones
respond to biomechanical stimuli is attributed to what is now referred to as Wolff's
Law of bone remodeling [ 40 ]. Bone structure adapts in response to the loading
environment; regions of lower stress are resorbed, leading to a net bone loss, and
regions of higher stresses are reinforced, leading to a net increase in bone. This
results in bone trabeculae that are aligned with the direction of principal stresses.
Studies in bone demonstrated that cortical thickness and trabecular architecture are
both modulated by the loading environment [ 41 , 42 ]. For example, astronauts lose
2% of hip bone density per month in space and tennis players have increased bone
density in their dominant arm [ 43 , 44 ]. While it is clear that mechanical forces are