BIOCHEMISTRY OF CONNECTIVE TISSUE.
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Connective tissue
Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial,
http://www.youtube.com/watch?v=WNd6H7l4sOI
http://www.youtube.com/watch?v=KED6BHVM97s&feature=related
and nervous tissue.)
Example of nervous
tissue
It
is largely a category of exclusion rather than one with a precise definition,
but all or most tissues in this category are similarly:
Organs derived from
mesoderm
·
Involved in structure and
support.
Human
blood smear:
a - erythrocytes;
b - neutrophil;
c - eosinophil;
d - lymphocyte.
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At the left the bracket indicates the hyaline cartilage. At the right this
tissue is more highly magnified. The chondrocytes
(A) are located in lacunae (C).
The matrix (B) contain collagen
fibers that are so fine they are not visible in tissue preparations.
Locations: "C" rings in the trachea, nose, articular ends of
bones, fetal skeleton
Function: precursor to bone, support
ELASTIC
CARTILAGE
Elastic cartilage is contained within the bracket at the left. This tissue
is more highly magnified at the right. The chondrocytes
(A) are contained in lacunae (C).
The matrix (B) contains abundant
elastic fibers.These fibers give great flexibility to this tissue.
FIBROCARTILAGE
These micrographs are of intervertebral disc tissue. At the left fibrocartilage
is found in the area between the parallel lines. This cartilage type is
recognized by chondrocytes (A)
oriented in rows. Even when the
tissue is highly magnified (as at the right), the lacunae, which hold the
chondrocytes, are not visible. The matrix
(B) contains numerous fine collagen fibers. These fibers give the tissue
durability.
Locations: ear, auditory canal, epiglottis
Functions: flexible support
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BONE
In the compact bone micrograph at the left, several complete osteons are
visible. In the center of the osteon is the central canal (A) which hold the blood vessels and a nerve. These
canals are surrounded by concentric rings of inorganic matrix, the lamellae (B). Between the lamellae are bone cells, the osteocytes (C) located in lacunae. Nutrients diffuse from cell to
cell through the canaliculi (D).
Location: skeleton
Function: framework, protection are usually considered connective tissue, but
because they differ so substantially from the other tissues in this class, the
phrase "connective tissue proper" is commonly used to exclude those
three. There is also variation in the classification of embryonic connective
tissues; on this page they will be treated as a third and separate category.
Classification
The types of connective tissue proper vary in the type and arrangement
of the fibers included and the type of "ground substance" or matrix.
The most common cell in these tissues is the fibroblast. (The nuclei stain
easily.) The tissues included here are:
AREOLAR
CONNECTIVE
In the watery matrix (ground substance) observe the nuclei of fibroblasts (A), collagen fibers (B) and elastic
fibers (C). Locations: beneath the skin and around blood vessels, muscles and
nerves Functions: binds one tissue to another (as skin connects to muscle),
protection and nourishment to the organs and structures it binds, and stores
"body fluid" |
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NSE REGULAR CONNECTIVE
The micrograph
above is at very low magnification. To the left, at a much higher
magnification, the fibroblasts (A) are
more clearly observed between the parallel collagenous
fibers (B).
Locations:
tendons and ligaments
Functions: strong flexible support
This section of aorta shows a tremendous number of elastic fibers (A). The fibroblasts are
not visible. The light pink in this tissue is smooth muscle. |
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Observe that the reticular fibers
(A) form a network or lattice in this spleen tissue. Do not confuse this
tissue with the elastic connective tissue seen above which has fibers that are parallel. Locations: spleen, lymph nodes, liver Function: gives support to soft organs
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ADIPOSE
Above observe adipose at a low magnification. The cells appear empty.
At the left observe that the nuclus (A) is pushed to the side of the cell giving
the cell the appearance of a signet ring. Cells are filled with fat globules (B). Locations/functions: |
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Connective
tissue proper
Areolar (or loose) connective tissue holds organs and epithelia in place, and has a variety of proteinaceous
fibres, including collagen and elastin.
It is also important in inflammation
·
Adipose tissue
contains adipocytes,
used for cushioning, thermal insulation,
lubrication
(primarily in the pericardium)
and energy
storage. [fat]
·
Dense
connective tissue (or, less
commonly, fibrous connective tissue) forms ligaments
and tendons.
Its densely packed collagen fibres have great tensile strength.
·
Reticular connective tissue is a network of reticular fibres (fine collagen, type III) that form a
soft skeleton to support the lymphoid
organs (lymph nodes,
bone marrow,
and spleen.)
Specialized connective tissues
·
Blood
functions in transport. Its extracellular matrix is blood plasma,
which transports dissolved nutrients,
hormones,
and carbon dioxide
in the form of bicarbonate.
The main
cellular component is red blood cells.
·
Bone
makes up virtually the entire skeleton in adult vertebrates.
·
Cartilage
makes up virtually the entire skeleton in chondrichthyes.
In most other vertebrates,
it is found primarily in joints,
where it provides cushioning. The extracellular matrix of cartilage is composed
primarily of collagen.
http://www.youtube.com/watch?v=WNd6H7l4sOI
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As the name implies, connective tissue
serves a "connecting" function. It supports and binds other tissues.
Unlike epithelial tissue, connective tissue typically has cells scattered
throughout an extracellular matrix.
Epithelial
Cell
The cells of connective tissue are
embedded in a great amount of extracellular material. This matrix is secreted by
the cells. It consists of protein fibers embedded in an amorphous mixture of
huge protein-polysaccharide ("proteoglycan") molecules.
Supporting connective tissue
Gives strength, support, and protection to the soft parts of the body.
·
Cartilage. Example: the outer ear
·
Bone. The matrix of bone contains
collagen fibers and mineral deposits. The most abundant mineral is calcium
phosphate, although magnesium, carbonate, and fluoride ions are also present.
Binding
connective tissue
It
binds body parts together.
·
Tendons connect muscle to bone. The matrix
is principally collagen,
and the fibers are all oriented parallel to each other. Tendons are strong but not elastic.
·
Ligaments attach one bone to another. They
contain both collagen and also the protein elastin.
Elastin
permits ligaments to be stretched.
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Fibrous connective tissue
It is distributed throughout the body. It serves
as a packing and binding material for most of our organs. Collagen, elastin,
and other proteins are found in the matrix.
Fascia is fibrous connective tissue that binds muscle together and binds the
skin to the underlying structures. Elastin
is a major protein component.
Adipose tissue is fibrous connective tissue in which the cells, called adipocytes,
have become almost filled with oil.
Fibrous and binding connective tissue is derived from cells called fibroblasts, which secrete the
extracellular matrix.
The extracellular matrix of cartilage and bone is secreted by
specialized cells derived from fibroblasts:
·
chondroblasts for cartilage;
·
osteoblasts for bone.
Composition of the ECM
The
ECM of vertebrates is composed of complex mixtures of
·
proteins and proteoglycans,
·
in the case of bone,
mineral deposits.
Proteins
Almost
all of the proteins are glycoproteins;
that is, have short chains of carbohydrate residues attached to them. (Elastin does not.) A wide variety of collagens. [Link to a page devoted to
the collagens.]
·
Laminins. Abundant in the basal lamina of epithelia.
·
Fibronectin. Binds cells to the ECM.
·
Elastins. Provide flexibility to skin,
arteries, and lungs. (These are not glycosylated.)
Proteoglycans
Proteoglycans are also glycoproteins but consist of much more
carbohydrate than protein; that is, they are huge clusters of carbohydrate
chains often attached to a protein backbone.
·
The protein backbone of
proteoglycans is synthesized, like other secreted proteins, in the endoplasmic reticulum.
·
Several sugars are
incorporated in proteoglycans. The most abundant one is N-acetylglucosamine (NAG) (the same monomer out
of which chitin is made).
·
The long chains of sugar
residues are attached to serine residues in the protein backbone; that is, they
are "O-linked".
·
This glycosylation occurs
in the Golgi apparatus.
·
Sulfate groups are also added to the sugars
while in the Golgi apparatus.
·
In most cases the completed
molecules are then secreted by the cell.
Some examples:
·
Chondroitin sulfate
·
Heparan sulfate
·
Keratan sulfate
·
Hyaluronic acid (This one contains
literally thousands of NAG residues but does not have a protein component.)
(Their
presence in connective tissue like joints accounts for the popularity of
N-acetylglucosamine and chondroitin sulfate as dietary supplements for
arthritis sufferers.)
Proteoglycans
are degraded in lysosomes. A variety of different enzymes are needed. Inherited
deficiencies in any one of these produces one of some dozen different types of mucopolysaccharidosis (mucopolysaccharide is the earlier name for proteoglycan).
Syndecan-1
This proteoglycan differs from the others in being retained at the
surface of the cell anchored in the plasma membrane as an integral transmembrane protein.
Syndecan-1 binds chemokines (chemotactic cytokines). When epithelia are damaged, these complexes are released and diffuse
away forming a chemotactic gradient that attracts neutrophils to the site. Thus syndecan-1 plays a crucial
role in inflammation.
Connecting Cells to the
ECM
Most
normal vertebrate cells cannot survive unless they are anchored to the
extracellular matrix. This anchorage
dependence is often lost when a cell turns cancerous. (HeLa cells,
for example, are among the few types of vertebrate cell that can be grown in
liquid culture.)
Cells
attach to the ECM by means of transmembrane glycoproteins called integrins.
·
The extracellular portion
of integrins binds to various types of ECM proteins:
·
collagens
·
laminins
·
fibronectin
·
The intracellular portion
binds to the actin filaments
of the cytoskeleton.
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Cancer Metastasis
Cancers
begin as a primary tumor. At some point, however, cells break away from the
primary tumor and - traveling in blood and lymph - establish metastases
in other locations of the body. Metastasis is what usually kills the patient.
In order to enter (and exit) the blood or lymph, cancer cells must pass
through a basement membrane. They are able to do so by secreting proteinases
(including serine proteases)
that digest a path for them.
Loose Connective Tissue
In vertebrates, the most common type of
connective tissue is loose connective tissue. It holds organs in place and attaches
epithelial tissue to other underlying tissues.
Loose connective tissue is named based on the "weave" and type of its
constituent fibers. There are three main types:
Collagenous fibers
are
made of collagen
and consist of bundles of fibrils that are coils of collagen molecules.
Elastic Fibers
Elastic fibers are made of elastin and are "stretchable."
Reticular Fibers
Reticular fibers join connective tissues to other tissues.
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Fibrous Connective Tissue
Another
type of connective tissue is fibrous connective tissue which is found in tendons and ligaments. Fibrous connective tissue is
composed of large amounts of closely packed collagenous fibers.
Specialized
Connective Tissues
Adipose tissue is a form of loose connective tissue that stores fat.
Cartilage is a form of fibrous connective tissue that is composed
of closely packed collagenous fibers in a rubbery gelatinous substance called
chondrin. The skeletons of sharks and human embryos are composed of cartilage.
Cartilage also provides flexible support for certain structures in adult humans
including the nose, trachea and ears.
Bone is a type of mineralized connective tissue that
contains collagen and calcium phosphate, a mineral crystal. Calcium phosphate
gives bone its firmness.
Interestingly enough, blood is considered to be a type of connective tissue. Even
though it has a different function in comparison to other connective tissues it
does have an extracellular matrix. The matrix is the plasma and erythrocytes, leukocytes and platelets are suspended in the plasma.
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Human Blood Cells |
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Embryonic connective
tissues
·
Mesenchymal
connective tissue
Fiber types
Fiber
types as follows:
Disorders of connective tissue
Various
connective tissue conditions have been identified; these can be both inherited
and environmental.
·
Marfan syndrome
- a genetic disease causing abnormal fibrillin.
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·
Scurvy
- caused by a dietary deficiency in vitamin C,
leading to abnormal collagen.
·
Ehlers-Danlos syndrome - deficient type III collagen- a genetic disease causing progressive
deterioration of collagens, with different EDS types affecting different sites
in the body, such as joints, heart valves, organ walls, arterial walls, etc.
A representation
of a condensed eukaryotic chromosome, as seen during cell division.
·
Loeys-Dietz syndrome - a genetic disease related to Marfan syndrome, with an emphasis on
vascular deterioration.
·
Systemic lupus erythematosus - a chronic, multisystem, inflammatory disorder of probable autoimmune
etiology, occurring predominantly in young women.
·
Osteogenesis imperfecta (brittle bone disease) - caused by insufficient production of good
quality collagen to produce healthy, strong bones.
·
Fibrodysplasia ossificans progressiva - disease of the connective tissue, caused by a defective gene which
turns connective tissue into bone.
·
Spontaneous pneumothorax
- collapsed lung, believed to be related to subtle abnormalities in connective
tissue.
·
Sarcoma - a neoplastic
process originating within connective tissue.
Staining of connective
tissue
For microscopic viewing, the majority of the connective tissue staining
techniques color tissue fibers in contrasting shades. Collagen may be
differentially stained by any of the following techniques:
·
Van Gieson's
stain
·
Masson's
Trichrome stain
Microscopy
of keratin filaments inside cells.
·
Mallory's
Aniline Blue stain
·
Azocarmine
stain
·
Krajian's
Aniline Blue stain
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