Musculoskeletal Disorders. Sean Gallagher
known as a motor end plate) (Figure 3.11). Within this axon terminal are numerous synaptic vesicles containing the neurotransmitter acetylcholine. When a somatic neuron fires and the action potential reaches the motor end plate, acetylcholine is released into a synaptic cleft (a space between the axonal terminal and the muscle). The synaptic cleft is a highly folded region of the sarcolemma that allows for more surface area. There are numerous mitochondria, ribosomes, and glycogen granules at this site. When acetylcholine binds to its receptor, Na+ channels open and membrane depolarization results. Excess acetylcholine in the synaptic cleft is hydrolyzed by the enzyme cholinesterase to avoid prolonged contact of the neurotransmitter with its receptors. The depolarization is then propagated deep into the myofiber by the previously discussed transverse tubule system. At each triad (a T‐tubule and two cisterna), the depolarization signal is passed to the sarcolemma reticulum. This results in a release of Ca2+ and initiation of the muscle cells’s contraction cycle. When the depolarization ceases, the Ca2+ is actively transported back into the cisterna for storage, and the muscle cell relaxes.
Figure 3.10 The sliding‐filament mechanism.
Tortora, G. J., & Derrickson, B. H. (Eds.), (2010). Muscle. In Introduction to the human body, 11th ed., Wiley.
Extracellular matrix/fascia
As previously mentioned and depicted (Figures 3.3 and 3.6), individual muscle fibers are bound together by a complex system of collagenous supporting tissue that link individual myofibers into a fascicle in order to form a single functional mass (Gillies & Lieber, 2011). The size of the fasciculi reflects the function of a muscle. Muscles responsible for fine controlled movements, like those of the hand, have small fasciculi and a relatively greater proportion of perimysial supporting tissue. Larger muscles responsible for gross movements have large fascicles and relatively little perimysial tissue. Muscle fibers are also anchored by these fascial connective tissues. The external lamina transmits the contractile forces developed by the internal contractile proteins. The connective tissue framework becomes continuous with those of tendons, as well as bone or skin when muscles are directly attached to these latter structures. The extracellular matrix also serves as a biological reservoir of muscle stem cells. In both injured and diseased states, the extracellular matrix adapts dramatically, a property that has clinical manifestations for muscle function.
Figure 3.11 The neuromuscular junction. Adult skeletal muscle is highly organized with one neuronal branch innervating each myofiber at the neuromuscular junction, which exhibits a mature, pretzel morphology with direct overlap between the presynaptic nerve terminal bouton and the postsynaptic acetylcholine receptor clusters.
Gilbert‐Honick, J. & Grayson, W. (2020). Vascularized and innervated skeletal muscle tissue engineering. Advanced Healthcare Materials 9(1): e1900626. Wiley.
Muscle as an endocrine system
Skeletal muscle is also an endocrine system and serves as a major site of insulin‐stimulated glucose disposal and homeostasis (Mukund & Subramaniam, 2019). It secretes a variety of cytokines and peptides, termed “myokines,” including interleukin (IL)‐8, IL‐18, IL‐15, insulin like growth factor 1 (IGF1), and fibroblast growth factor 21 (FGF21). These factors are regulated by muscle contractile activity and exercise. These myokines exert autocrine (self), paracrine (related only to the local vicinity of the organ producing the factor), and endocrine (systemic signaling) effects in a context‐dependent manner that enables muscles to maintain metabolic homeostasis during health and exercise, and responses during chronic metabolic conditions and disorders. This will be discussed further in Chapters 11 and 15.
Tendon
Tendons are a type of dense regular connective tissue since they are arranged in a highly organized pattern with a clear predominance of collagen fibers over ground substance and cell numbers. They can also be thought of as a fibrous cord or band of variable length that anchor muscles to bone. Many muscles have two tendons at both their proximal and distal ends (such as the biceps muscle of the upper extremity), although some muscles attach directly to bone without a tendon (such as the proximal attachments of deep flexor and extensor muscles on the radius and ulna). Tendons may unit with muscles at the end of a muscle, or it may run along the side of the muscle or within its center for long or short distances, receiving muscle fibers along its lateral border. The point of union with a muscle is called a myotendinous junction (Kannus, 2000). Although tendons are characterized by their great tensile strength (Benjamin & Ralphs, 1998), they have dynamic characteristics that belie their appearance and respond to exercise or immobilization by altering their tensile strength (Woo & Buckwalter, 1988). Aponeuroses are similar in structure to tendons, although they are thinner sheet‐like structures and connect one muscle to another muscle or to bone. The overall characteristics of tendons are summarized in Table 3.3.
Tendon Structure
Cells
A variety of distinctive cell types occur within tendons. Tenocytes are transformed from tenoblasts (immature tenocytes), which are rounded cells with large, ovoid nuclei (Borynsenko & Beringer, 1989). Tenocytes are flat tapered cells that appear spindle‐shaped in longitudinal tissue sections and stellate (with long extensions) in cross sections. Tenocytes, a common synonym for differentiated fibroblast‐like cells that lie within rows within the tendon proper, comprise about 95% of the cellular elements of a tendon. They lie sparingly in longitudinal rows between collagen fibrils (Figure 3.12) (Butler, Grood, Noyes, & Zernicke, 1978) and are aligned in parallel with the primary direction of force on the tendon. Tenocytes synthesize collagen and most other compounds of a tendon’s extracellular matrix (Evans & Barbenel, 1975; Kjaer, 2004). Tendons also contain low numbers of stem/progenitor cells (tendon stem/progenitor cells, which are also regarded as tendon‐derived stem cells). These cells show typical stem cell characteristics of self‐renewal capacity (Li, Wu, & Liu, 2021). In tendon fascial sheaths, there are also different subpopulations of fibroblasts with different roles in matrix synthesis and cell migration during wound healing (Jozsa & Kannus, 1997). The remaining 5–10% of cells in a tendon includes chondrocytes (located at entheses, where the tendon attaches to bone, Figure 3.12c), endothelial cells associated with blood vessels, and peripheral glial cells associated with nerve processes. In pathological conditions and during wound healing, inflammatory cells (neutrophils, macrophages, and lymphocytes) and myofibroblasts can be observed in tendon tissues (Barbe et al., 2021; Fedorczyk et al., 2010; Jozsa & Kannus, 1997; Kietrys, Barr, & Barbe, 2011).
Table 3.3 Summary of Cells, Extracellular Matrix (ECM), Subregions, and Function Of Tendons Under Normal Conditions
| Characteristic | Description |
|---|---|
| Tissue type |
Dense regular |