A tendon or sinew is a tough, high-tensile-strength band of
dense fibrous connective tissue that connects
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
to
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability to withstand significant amounts of
tension
Tension may refer to:
Science
* Psychological stress
* Tension (physics), a force related to the stretching of an object (the opposite of compression)
* Tension (geology), a stress which stretches rocks in two opposite directions
* Voltage or el ...
.
Tendons are similar to
ligaments
A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the:
* Peritoneal li ...
; both are made of
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
. Ligaments connect one bone to another, while tendons connect muscle to bone.
Structure
Histologically
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
, tendons consist of
dense regular connective tissue
Dense regular connective tissue (DRCT) provides connection between different tissues in the human body. The collagen fibers in dense regular connective tissue are bundled in a parallel fashion. DRCT is divided into white fibrous connective tissue ...
. The main cellular component of tendons are specialized
fibroblast
A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s called
tendon cell
Vertebrates
Tendon cells, or tenocytes, are elongated fibroblast type cells. The cytoplasm is stretched between the collagen fibres of the tendon. They have a central cell nucleus with a prominent nucleolus. Tendon cells have a well-developed ...
s (tenocytes). Tenocytes synthesize the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
of tendons, abundant in densely packed
collagen fibers
Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers.
It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endo ...
. The collagen fibers are parallel to each other and organized into tendon fascicles. Individual fascicles are bound by the
endotendineum, which is a delicate loose connective tissue containing thin collagen fibrils and elastic fibres. Groups of fascicles are bounded by the
epitenon
A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...
, which is a sheath of
dense irregular connective tissue
Dense irregular connective tissue has fibers that are not arranged in parallel bundles as in dense regular connective tissue.
Dense irregular connective tissue consists of mostly collagen fibers. It has less ground substance than loose connecti ...
. The whole tendon is enclosed by a
fascia
A fascia (; plural fasciae or fascias; adjective fascial; from Latin: "band") is a band or sheet of connective tissue, primarily collagen, beneath the skin that attaches to, stabilizes, encloses, and separates muscles and other internal organs. ...
. The space between the fascia and the tendon tissue is filled with the
paratenon, a fatty
areolar tissue
Loose connective tissue, sometimes called areolar tissue, is a cellular connective tissue with thin and relatively sparse collagen fibers. Its ground substance occupies more volume than the fibers do. It has a viscous to gel-like consistenc ...
. Normal healthy tendons are anchored to bone by
Sharpey's fibres
Sharpey's fibres (bone fibres, or perforating fibres) are a Matrix (biology), matrix of connective tissue consisting of bundles of strong predominantly type I Collagen, collagen fibres connecting periosteum to bone. They are part of the outer fibr ...
.
Extracellular matrix
The dry mass of normal tendons, which makes up 30-45% of their total mass, is composed of:
* 60-85% collagen
**60-80% collagen I
**0-10% collagen III
**2% collagen IV
**small amounts of collagens V, VI, and others
* 15-40% non-collagenous extracellular matrix components, including:
**3%
cartilage oligomeric matrix protein
Cartilage oligomeric matrix protein (COMP), also known as thrombospondin-5, is an extracellular matrix (ECM) protein primarily present in cartilage. In humans it is encoded by the ''COMP'' gene.
Function
The protein encoded by this gene is a n ...
,
**1-2%
elastin
Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bod ...
,
** 1–5%
proteoglycans
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
,
** 0.2% inorganic components such as
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
,
manganese
Manganese is a chemical element with the symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of industrial alloy use ...
, and
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
.
[Jozsa, L., and Kannus, P., Human Tendons: Anatomy, Physiology, and Pathology. Human Kinetics: Champaign, IL, 1997.]
While
type I collagen
Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers.
It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endomy ...
makes up most of the collagen in tendon, many minor collagens are present that play vital roles in proper tendon development and function. These include type II collagen in the
cartilaginous
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and ...
zones, type III collagen in the
reticulin
Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a support ...
fibres of the vascular walls, type IX collagen, type IV collagen in the basement membranes of the
capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
, type V collagen in the vascular walls, and type X collagen in the mineralized fibrocartilage near the interface with the bone.
Ultrastructure and collagen synthesis
Collagen fibres coalesce into
macroaggregates. After secretion from the cell, cleaved by
procollagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
N- and C-
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s, the tropocollagen molecules spontaneously assemble into insoluble fibrils. A collagen molecule is about 300 nm long and 1–2 nm wide, and the diameter of the fibrils that are formed can range from 50–500 nm. In tendons, the fibrils then assemble further to form fascicles, which are about 10 mm in length with a diameter of 50–300 μm, and finally into a tendon fibre with a diameter of 100–500 μm.
The collagen in tendons are held together with
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...
(a compound consisting of a protein bonded to glycosaminoglycan groups, present especially in connective tissue) components including
decorin
Decorin is a protein that in humans is encoded by the ''DCN'' gene.
Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a p ...
and, in compressed regions of tendon,
aggrecan, which are capable of binding to the collagen fibrils at specific locations. The proteoglycans are interwoven with the collagen fibrils their
glycosaminoglycan
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
(GAG) side chains have multiple interactions with the surface of the fibrils showing that the proteoglycans are important structurally in the interconnection of the fibrils. The major GAG components of the tendon are
dermatan sulfate
Dermatan sulfate is a glycosaminoglycan (formerly called a mucopolysaccharide) found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs.
It is also referred to as chondroitin sulfate B, although it is no longer classifie ...
and
chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have ove ...
, which associate with collagen and are involved in the fibril assembly process during tendon development. Dermatan sulfate is thought to be responsible for forming associations between fibrils, while chondroitin sulfate is thought to be more involved with occupying volume between the fibrils to keep them separated and help withstand deformation. The dermatan sulfate side chains of decorin aggregate in solution, and this behavior can assist with the assembly of the collagen fibrils. When decorin molecules are bound to a collagen fibril, their dermatan sulfate chains may extend and associate with other dermatan sulfate chains on decorin that is bound to separate fibrils, therefore creating interfibrillar bridges and eventually causing parallel alignment of the fibrils.
Tenocytes
The
tenocytes
Vertebrates
Tendon cells, or tenocytes, are elongated fibroblast type cells. The cytoplasm is stretched between the collagen fibres of the tendon. They have a central cell nucleus with a prominent nucleolus. Tendon cells have a well-developed ...
produce the collagen molecules, which aggregate end-to-end and side-to-side to produce collagen fibrils. Fibril bundles are organized to form fibres with the elongated tenocytes closely packed between them. There is a three-dimensional network of cell processes associated with collagen in the tendon. The cells communicate with each other through
gap junctions
Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...
, and this signalling gives them the ability to detect and respond to mechanical loading. These communications happen by two proteins essentially :
connexin 43
Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the ''GJA1'' gene on chromosome 6. As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular co ...
, present where the cells processes meet and in cell bodies
connexin 32, present only where the processes meet.
Blood vessels may be visualized within the endotendon running parallel to collagen fibres, with occasional branching transverse
anastomoses
An anastomosis (, plural anastomoses) is a connection or opening between two things (especially cavities or passages) that are normally diverging or branching, such as between blood vessels, leaf veins, or streams. Such a connection may be normal ...
.
The internal tendon bulk is thought to contain no nerve fibres, but the epitenon and paratenon contain nerve endings, while
Golgi tendon organs
The Golgi tendon organ (GTO) (also called Golgi organ, tendon organ, neurotendinous organ or neurotendinous spindle) is a proprioceptor – a type of sensory receptor that senses changes in muscle tension. It lies at the interface between a musc ...
are present at the
myotendinous junction
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
between tendon and muscle.
Tendon length varies in all major groups and from person to person. Tendon length is, in practice, the deciding factor regarding actual and potential muscle size. For example, all other relevant biological factors being equal, a man with a shorter tendons and a longer biceps muscle will have greater potential for muscle mass than a man with a longer tendon and a shorter muscle. Successful
bodybuilders
Bodybuilding is the use of progressive resistance exercise to control and develop one's muscles (muscle building) by muscle hypertrophy for aesthetic purposes. It is distinct from similar activities such as powerlifting because it focuses ...
will generally have shorter tendons. Conversely, in sports requiring athletes to excel in actions such as running or jumping, it is beneficial to have longer than average
Achilles tendon
The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcaneus (h ...
and a shorter
calf muscle
The triceps surae consists of two muscles located at the calf – the two-headed gastrocnemius and the soleus. These muscles both insert into the calcaneus, the bone of the heel of the human foot, and form the major part of the muscle of the ...
.
Tendon length is determined by genetic predisposition, and has not been shown to either increase or decrease in response to environment, unlike muscles, which can be shortened by trauma, use imbalances and a lack of recovery and stretching. In addition tendons allow muscles to be at an optimal distance from the site where they actively engage in movement, passing through regions where space is premium, like the
carpal tunnel
In the human body, the carpal tunnel or carpal canal is the passageway on the palmar side of the wrist that connects the forearm to the hand.
The tunnel is bounded by the bones of the wrist and flexor retinaculum from connective tissue. Normall ...
.
Functions
![Magnified view of a Tendon](https://upload.wikimedia.org/wikipedia/commons/e/ea/Magnified_view_of_a_Tendon.jpg)
Traditionally, tendons have been considered to be a mechanism by which muscles connect to bone as well as muscles itself, functioning to transmit forces. This connection allows tendons to passively modulate forces during locomotion, providing additional stability with no active work. However, over the past two decades, much research has focused on the elastic properties of some tendons and their ability to function as springs. Not all tendons are required to perform the same functional role, with some predominantly positioning limbs, such as the fingers when writing (positional tendons) and others acting as springs to make locomotion more efficient (energy storing tendons). Energy storing tendons can store and recover energy at high efficiency. For example, during a human stride, the Achilles tendon stretches as the ankle joint dorsiflexes. During the last portion of the stride, as the foot plantar-flexes (pointing the toes down), the stored elastic energy is released. Furthermore, because the tendon stretches, the muscle is able to function with less or even
no change in length, allowing the muscle to generate more force.
The mechanical properties of the tendon are dependent on the collagen fiber diameter and orientation. The collagen fibrils are parallel to each other and closely packed, but show a wave-like appearance due to planar undulations, or crimps, on a scale of several micrometers. In tendons, the collagen fibres have some flexibility due to the absence of hydroxyproline and proline residues at specific locations in the amino acid sequence, which allows the formation of other conformations such as bends or internal loops in the triple helix and results in the development of crimps. The crimps in the collagen fibrils allow the tendons to have some flexibility as well as a low compressive stiffness. In addition, because the tendon is a multi-stranded structure made up of many partially independent fibrils and fascicles, it does not behave as a single rod, and this property also contributes to its flexibility.
The proteoglycan components of tendons also are important to the mechanical properties. While the collagen fibrils allow tendons to resist tensile stress, the proteoglycans allow them to resist compressive stress. These molecules are very hydrophilic, meaning that they can absorb a large amount of water and therefore have a high swelling ratio. Since they are noncovalently bound to the fibrils, they may reversibly associate and disassociate so that the bridges between fibrils can be broken and reformed. This process may be involved in allowing the fibril to elongate and decrease in diameter under tension. However, the proteoglycans may also have a role in the tensile properties of tendon. The structure of tendon is effectively a fibre composite material, built as a series of hierarchical levels. At each level of the hierarchy, the collagen units are bound together by either collagen crosslinks, or the proteoglycans, to create a structure highly resistant to tensile load. The elongation and the strain of the collagen fibrils alone have been shown to be much lower than the total elongation and strain of the entire tendon under the same amount of stress, demonstrating that the proteoglycan-rich matrix must also undergo deformation, and stiffening of the matrix occurs at high strain rates. This deformation of the non-collagenous matrix occurs at all levels of the tendon hierarchy, and by modulating the organisation and structure of this matrix, the different mechanical properties required by different tendons can be achieved. Energy storing tendons have been shown to utilise significant amounts of sliding between fascicles to enable the high strain characteristics they require, whilst positional tendons rely more heavily on sliding between collagen fibres and fibrils. However, recent data suggests that energy storing tendons may also contain fascicles which are twisted, or helical, in nature - an arrangement that would be highly beneficial for providing the spring-like behaviour required in these tendons.
Mechanics
Tendons are
viscoelastic
In materials science and continuum mechanics, viscoelasticity is the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation. Viscous materials, like water, resist shear flow and strain linearly wi ...
structures, which means they exhibit both elastic and viscous behaviour. When stretched, tendons exhibit typical "soft tissue" behavior. The force-extension, or stress-strain curve starts with a very low stiffness region, as the crimp structure straightens and the collagen fibres align suggesting negative Poisson's ratio in the fibres of the tendon. More recently, tests carried out in vivo (through MRI) and ex vivo (through mechanical testing of various cadaveric tendon tissue) have shown that healthy tendons are highly anisotropic and exhibit a negative Poisson's ratio (
auxetic
Auxetics are structures or materials that have a negative Poisson's ratio. When stretched, they become thicker perpendicular to the applied force. This occurs due to their particular internal structure and the way this deforms when the sample i ...
) in some planes when stretched up to 2% along their length, i.e. within their normal range of motion. After this 'toe' region, the structure becomes significantly stiffer, and has a linear stress-strain curve until it begins to fail. The mechanical properties of tendons vary widely, as they are matched to the functional requirements of the tendon. The energy storing tendons tend to be more elastic, or less stiff, so they can more easily store energy, whilst the stiffer positional tendons tend to be a little more viscoelastic, and less elastic, so they can provide finer control of movement. A typical energy storing tendon will fail at around 12-15% strain, and a stress in the region of 100-150 MPa, although some tendons are notably more extensible than this, for example the superficial digital flexor in the
horse
The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...
, which stretches in excess of 20% when galloping. Positional tendons can fail at strains as low as 6-8%, but can have moduli in the region of 700-1000 MPa.
Several studies have demonstrated that tendons respond to changes in mechanical loading with growth and remodeling processes, much like
bone
A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
s. In particular, a study showed that disuse of the
Achilles tendon
The Achilles tendon or heel cord, also known as the calcaneal tendon, is a tendon at the back of the lower leg, and is the thickest in the human body. It serves to attach the plantaris, gastrocnemius (calf) and soleus muscles to the calcaneus (h ...
in rats resulted in a decrease in the average thickness of the collagen fiber bundles comprising the tendon.
In humans, an experiment in which people were subjected to a simulated micro-gravity environment found that tendon stiffness decreased significantly, even when subjects were required to perform restiveness exercises.
These effects have implications in areas ranging from treatment of bedridden patients to the design of more effective exercises for
astronauts
An astronaut (from the Ancient Greek (), meaning 'star', and (), meaning 'sailor') is a person trained, equipped, and deployed by a human spaceflight program to serve as a commander or crew member aboard a spacecraft. Although generally r ...
.
Healing
The tendons in the foot are highly complex and intricate. Therefore, the healing process for a broken tendon is long and painful. Most people who do not receive medical attention within the first 48 hours of the injury will suffer from severe swelling, pain, and a burning sensation where the injury occurred.
It was believed that tendons could not undergo matrix turnover and that tenocytes were not capable of repair. However, it has since been shown that, throughout the lifetime of a person, tenocytes in the tendon actively synthesize matrix components as well as enzymes such as
matrix metalloproteinases
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs ...
(MMPs) can degrade the matrix.
Tendons are capable of healing and recovering from injuries in a process that is controlled by the tenocytes and their surrounding extracellular matrix.
The three main stages of tendon healing are inflammation, repair or proliferation, and remodeling, which can be further divided into consolidation and maturation. These stages can overlap with each other. In the first stage, inflammatory cells such as
neutrophils
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
are recruited to the injury site, along with
erythrocytes
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
.
Monocytes
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...
and
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
are recruited within the first 24 hours, and
phagocytosis
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
of
necrotic
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
materials at the injury site occurs. After the release of
vasoactive
A vasoactive substance is an endogenous agent or pharmaceutical drug that has the effect of either increasing or decreasing blood pressure and/or heart rate through its vasoactivity, that is, vascular activity (effect on blood vessels). By adju ...
and
chemotactic
Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
factors,
angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
and the
proliferation of tenocytes are initiated. Tenocytes then move into the site and start to synthesize collagen III.
After a few days, the repair or proliferation stage begins. In this stage, the tenocytes are involved in the synthesis of large amounts of collagen and proteoglycans at the site of injury, and the levels of GAG and water are high.
After about six weeks, the remodeling stage begins. The first part of this stage is consolidation, which lasts from about six to ten weeks after the injury. During this time, the synthesis of collagen and GAGs is decreased, and the cellularity is also decreased as the tissue becomes more fibrous as a result of increased production of collagen I and the fibrils become aligned in the direction of mechanical stress.
The final maturation stage occurs after ten weeks, and during this time there is an increase in crosslinking of the collagen fibrils, which causes the tissue to become stiffer. Gradually, over about one year, the tissue will turn from fibrous to scar-like.
Matrix metalloproteinases (MMPs) have a very important role in the degradation and remodeling of the ECM during the healing process after a tendon injury. Certain MMPs including MMP-1, MMP-2, MMP-8, MMP-13, and MMP-14 have collagenase activity, meaning that, unlike many other enzymes, they are capable of degrading collagen I fibrils. The degradation of the collagen fibrils by MMP-1 along with the presence of denatured collagen are factors that are believed to cause weakening of the tendon ECM and an increase in the potential for another rupture to occur. In response to repeated mechanical loading or injury,
cytokines
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
may be released by tenocytes and can induce the release of MMPs, causing degradation of the ECM and leading to recurring injury and chronic tendinopathies.
A variety of other molecules are involved in tendon repair and regeneration. There are five growth factors that have been shown to be significantly upregulated and active during tendon healing:
insulin-like growth factor 1
Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.
IGF-1 is a protein that in humans is ...
(IGF-I),
platelet-derived growth factor
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...
(PDGF),
vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
(VEGF),
basic fibroblast growth factor
Fibroblast growth factor 2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the ''FGF2'' gene. It binds to and exerts effects via specific fibroblast growth factor receptor '' ...
(bFGF), and
transforming growth factor beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
(TGF-β).
These growth factors all have different roles during the healing process. IGF-1 increases collagen and proteoglycan production during the first stage of inflammation, and PDGF is also present during the early stages after injury and promotes the synthesis of other growth factors along with the synthesis of DNA and the proliferation of tendon cells.
The three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) are known to play a role in wound healing and scar formation. VEGF is well known to promote angiogenesis and to induce endothelial cell proliferation and migration, and VEGF mRNA has been shown to be expressed at the site of tendon injuries along with collagen I mRNA. Bone morphogenetic proteins (BMPs) are a subgroup of TGF-β superfamily that can induce bone and cartilage formation as well as tissue differentiation, and BMP-12 specifically has been shown to influence formation and differentiation of tendon tissue and to promote fibrogenesis.
Effects of activity on healing
In animal models, extensive studies have been conducted to investigate the effects of mechanical strain in the form of activity level on tendon injury and healing. While stretching can disrupt healing during the initial inflammatory phase, it has been shown that controlled movement of the tendons after about one week following an acute injury can help to promote the synthesis of collagen by the tenocytes, leading to increased tensile strength and diameter of the healed tendons and fewer adhesions than tendons that are immobilized. In chronic tendon injuries, mechanical loading has also been shown to stimulate fibroblast proliferation and collagen synthesis along with collagen realignment, all of which promote repair and remodeling.
To further support the theory that movement and activity assist in tendon healing, it has been shown that immobilization of the tendons after injury often has a negative effect on healing. In rabbits, collagen fascicles that are immobilized have shown decreased tensile strength, and immobilization also results in lower amounts of water, proteoglycans, and collagen crosslinks in the tendons.
Several
mechanotransduction
In cellular biology, mechanotransduction ('' mechano'' + '' transduction'') is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of ...
mechanisms have been proposed as reasons for the response of tenocytes to mechanical force that enable them to alter their gene expression, protein synthesis, and cell phenotype, and eventually cause changes in tendon structure. A major factor is mechanical deformation of the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
, which can affect the
actin cytoskeleton
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other ...
and therefore affect cell shape, motility, and function. Mechanical forces can be transmitted by focal adhesion sites,
integrins
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
, and cell-cell junctions. Changes in the actin cytoskeleton can activate integrins, which mediate “outside-in” and “inside-out” signaling between the cell and the matrix.
G-proteins
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their ac ...
, which induce intracellular signaling cascades, may also be important, and ion channels are activated by stretching to allow ions such as calcium, sodium, or potassium to enter the cell.
Society and culture
Sinew was widely used throughout
pre-industrial
Pre-industrial society refers to social attributes and forums of political and cultural organization that were prevalent before the advent of the Industrial Revolution, which occurred from 1750 to 1850. ''Pre-industrial'' refers to a time before ...
eras as a tough, durable
fiber
Fiber or fibre (from la, fibra, links=no) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often incorporate ...
. Some specific uses include using sinew as
thread for sewing, attaching feathers to arrows (see
fletch), lashing tool blades to shafts, etc. It is also recommended in survival guides as a material from which strong cordage can be made for items like traps or living structures. Tendon must be treated in specific ways to function usefully for these purposes.
Inuit
Inuit (; iu, ᐃᓄᐃᑦ 'the people', singular: Inuk, , dual: Inuuk, ) are a group of culturally similar indigenous peoples inhabiting the Arctic and subarctic regions of Greenland, Labrador, Quebec, Nunavut, the Northwest Territories ...
and other
circumpolar people utilized sinew as the only cordage for all domestic purposes due to the lack of other suitable fiber sources in their ecological habitats. The elastic properties of particular sinews were also used in
composite recurved bows favoured by the steppe nomads of Eurasia, and Native Americans. The first stone throwing artillery also used the elastic properties of sinew.
Sinew makes for an excellent cordage material for three reasons: It is extremely strong, it contains natural glues, and it shrinks as it dries, doing away with the need for knots.
Culinary uses
Tendon (in particular,
beef
Beef is the culinary name for meat from cattle (''Bos taurus'').
In prehistoric times, humankind hunted aurochs and later domesticated them. Since that time, numerous breeds of cattle have been bred specifically for the quality or quantity ...
tendon) is used as a food in some Asian cuisines (often served at
yum cha
''Yum cha'' is the Cantonese tradition of brunch involving Chinese tea and ''dim sum.'' The practice is popular in Cantonese-speaking regions, including Guangdong province, Guangxi province, Hong Kong, and Macau. It is also carried out in other ...
or
dim sum restaurants). One popular dish is ''suan bao niu jin'', in which the tendon is marinated in garlic. It is also sometimes found in the Vietnamese noodle dish
phở
Phở or pho (, , ; ) is a Vietnamese soup dish consisting of broth, rice noodles (), herbs, and meat (usually beef (), sometimes chicken ()). Phở is a popular food in Vietnam where it is served in households, street stalls and restaurants co ...
.
Clinical significance
Injury
Tendons are subject to many types of injuries. There are various forms of
tendinopathies or tendon injuries due to overuse. These types of injuries generally result in inflammation and degeneration or weakening of the tendons, which may eventually lead to tendon rupture.
Tendinopathies can be caused by a number of factors relating to the tendon extracellular matrix (ECM), and their classification has been difficult because their symptoms and histopathology often are similar.
The first category of tendinopathy is paratenonitis, which refers to inflammation of the paratenon, or paratendinous sheet located between the tendon and its sheath.
Tendinosis
Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbo ...
refers to non-inflammatory injury to the tendon at the cellular level. The degradation is caused by damage to collagen, cells, and the vascular components of the tendon, and is known to lead to rupture. Observations of tendons that have undergone spontaneous rupture have shown the presence of collagen fibrils that are not in the correct parallel orientation or are not uniform in length or diameter, along with rounded tenocytes, other cell abnormalities, and the ingrowth of blood vessels.
Other forms of tendinosis that have not led to rupture have also shown the degeneration, disorientation, and thinning of the collagen fibrils, along with an increase in the amount of glycosaminoglycans between the fibrils.
The third is paratenonitis with tendinosis, in which combinations of paratenon inflammation and tendon degeneration are both present. The last is
tendinitis
Tendinopathy, a type of tendon disorder that results in pain, swelling, and impaired function. The pain is typically worse with movement. It most commonly occurs around the shoulder (rotator cuff tendinitis, biceps tendinitis), elbow (tennis elbo ...
, which refers to degeneration with inflammation of the tendon as well as vascular disruption.
Tendinopathies may be caused by several intrinsic factors including age, body weight, and nutrition. The extrinsic factors are often related to sports and include excessive forces or loading, poor training techniques, and environmental conditions.
Other animals
![Edmontosaurus ossified tendon](https://upload.wikimedia.org/wikipedia/commons/2/24/Edmontosaurus_ossified_tendon.JPG)
In some organisms, notably
bird
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...
s, and
ornithischia
Ornithischia () is an extinct order of mainly herbivorous dinosaurs characterized by a pelvic structure superficially similar to that of birds. The name ''Ornithischia'', or "bird-hipped", reflects this similarity and is derived from the Greek s ...
n
dinosaur
Dinosaurs are a diverse group of reptiles of the clade Dinosauria. They first appeared during the Triassic period, between 243 and 233.23 million years ago (mya), although the exact origin and timing of the evolution of dinosaurs is t ...
s,
portions of the tendon can become ossified. In this process, osteocytes infiltrate the tendon and lay down bone as they would in sesamoid bone such as the patella. In birds, tendon ossification primarily occurs in the hindlimb, while in ornithischian dinosaurs, ossified axial muscle tendons form a latticework along the neural and haemal spines on the tail, presumably for support.
See also
*
Aponeurosis
An aponeurosis (; plural: ''aponeuroses'') is a type or a variant of the deep fascia, in the form of a sheet of pearly-white fibrous tissue that attaches sheet-like muscles needing a wide area of attachment. Their primary function is to join musc ...
*
Cartilage
Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...
*
Chordae tendineae
The chordae tendineae (tendinous cords), colloquially known as the heart strings, are inelastic cords of fibrous connective tissue that connect the papillary muscles to the tricuspid valve and the mitral valve in the heart.
Structure
The chordae ...
*
List of muscles of the human body
This is a table of skeletal muscles of the human anatomy.
There are around 650 skeletal muscles within the typical human body. Almost every muscle constitutes one part of a pair of identical bilateral symmetry, bilateral muscles, found on both ...
*
Tendon sheath
A tendon sheath is a layer of synovial membrane around a tendon. It permits the tendon to stretch and not adhere to the surrounding fascia.
It has two layers:
* synovial sheath
A synovial sheath is one of the two membranes of a tendon sheath wh ...
References
{{Authority control
Soft tissue
Skeletal system
*