GENIUS UNIVERSITY

FACULTY OF DENTISTRY
GENERAL HISTOLOGY 1
1st Year
1st term
2020/2021

Connective tissue 2

Lecture. No. 8

BY

Assis. Prof/ Abdulrazzaq AL-Maweri

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Extracellular matrix (ground substances+ fibers):

The Ground Substances:

- The ground substance is mainly water (remember that the connective
tissue acts as a transport medium for gases, small molecules and waste
products between blood vessels and epithelium for example).
- It’s not only water because according to gravity, this water will pool
down in the lower part of the body so in fact it’s a gel-like structure.
- The ground substance is mainly water, but this water is stabilized by
macromolecules (called stabilizing macromolecules), it functions like
a jelly, it transforms water from liquid state to viscous state. For
example, in blood (special type of c.t), the ground substance lacks
stabilizing macromolecules and lacks fibers, so the extracellular
matrix is fluid
- With different types of C.T we’ll see different components of ECM
(like in blood its ECM is fluid but in bone it’s solid because it is
calcified), but here the lecture about ORDANIRY C.T which is
located directly under epithelium not about special types of C.T.

- Three types of ground substances (macromolecules):

1. Glycosaminoglycan(GAGs)
2. Proteoglycans
3. Glycoproteins

1. GAGs:
✓ Long chains of repeating units of disaccharides (2 sugars), unbranched
✓ 2 types:
- Sulfated: contain sulfate group such as (keratin sulfate, chondroitin
sulfate, dermatan sulfate, and heparan sulfate (heparin).
- Non-sulfated: No sulfate group, the only example is: hyaluronic acid
(hyaluronic acid is a long molecule with very high molecular weight).

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2- Proteoglycans: consist of proteins (~5%) and polysaccharide chains
(~95%). The polysaccharide chains belong to glycosaminoglycans (a protein
core attaches to many GAGs).
3-Glycoproteins: consist of proteins (~95%) and polysaccharide chains
(~5%). The sugar chains are branched short polysaccharides
(oligosacchardies, oligo= few).

- The hyaluronic acid acts as a backbone where the other

glycosaminoglycans are going to attach through a protein core, so
simply the hyaluronic acid interacts with proteoglycans
- Ground substance consists largely of proteoglycans and hyaluronic
acid. Proteoglycans are very large macromolecules, consisting of a
core protein to which many glycosaminoglycan (GAG) molecules are
attached. GAGs are long-chained polysaccharides made up of
repeating disaccharide units. GAGs are highly negatively charged
(polyanions). The high density of negative charges attracts water,
forming a hydrated gel. This gel permits the rapid diffusion of water-
soluble molecules but inhibits the movement of large molecules and
bacteria.
- The large structure formed by hyaluronic acid and proteoglycans
makes a spherical space; this space is called a domain. So bacteria
need to pass between these domains in order to pass through the
connective tissue, so that’s why we say that the ground substance has
filtering effect and prevents the spread of the bacteria. The
pathogenicity of a bacterium is indeed to some extent determined by
its ability to find its way through the mesh, and some of the more
invasive types produce the enzyme hyaluronidase, this enzyme is able
to destruct hyaluronic acid which will destruct this domain so they are
able to invade the connective tissue and the infection spreads
- Each domain looks like a Bottle Brush: the handle is hyaluronic acid
and the bristles are the proteoglycans

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 Clinical application: Hyaluronic dermal fillers are today’s most
popular and considered best dermal fillers. A dermal filler injection is
a material injected inside deep dermis.
Hyaluronic acid is a naturally occurring substance in the body that is
lost with aging. Hyaluronic acid dermal fillers add volume to the
facial structures (nasolabial fold, marionette lines). Remember
Hyaluronic acid is very hydrophillic and attracts water, and look very
natural. Hyaluronic acid fillers typically last 6to 12 months and can
also be used for lip augmentation.

- Functions of Proteoglycans
✓ Resistance of compression. - They are stabilizing
macromolecules (little amount of it gives water gel state).
✓ Retardation of movement of microorganisms.
✓ Act as a filter

Adhesive glycoproteins:

Laminin: connects the integrins of the hemidesmosomes with the other

components "other proteins" of extracellular matrix.
Chondronectin: it is found in cartilage. "chondro= " , "nectin means
connection".
The connection (adhesion) is between the cells of cartilage and ECM
Osteonectin: "osteo means bone".
Fibronectin: it is found in basal lamina, connection between cells and ECM.

Fibers of connective tissue:

1- Collagen fibers: the main function is to give strength.

2- Elastic fibers: give elasticity "elasticity means, the ability to restore the
original shape after distortion".
3- Reticular fibers: give a network.

- In any connective tissue we can find the three types of fibers,

but the proportions of these components differ.
- If the tissue is composed mainly of collagen type 1, we call it
collagenous connective tissue.

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 - If it's mainly composed of elastic fibers, we call it elastic connective
tissue.
- If it's mainly composed of reticular, we call it reticular connective
tissue.

*Collagen fibers:
We have many types of collagen fibers, each type has different distribution
than other types, we will mainly focus in collagen type one, which is the
strongest type of collagen.

- Collagen is a protein, 30% of the proteins in our body are collagen" it

is the most common protein in our body"

- Collagen fibers are very strong, to tear them you need hundreds of
kilograms per 1 cm2, leather for example consists of Collagenous
Fibers - fibers that originate from the skin of large mammals

- Collagen fibers are colorless, but the bulk accumulation of these fibers
appears white (for example the tendon is composed of collagen type 1,
grossly the tendon appears whitish). Birefringence

- With hematoxylin and eosin, collagen appears acidophilic (pink)

- If we want to find the connective tissue, we look for eosinophilia,

which is the collagen fibers; because the connective tissue is
composed of cells and extracellular matrix (ground substance "in the
section appears unstained").

- There are 28 kinds of collagen; each type has different sequence of

amino acids, different chains combinations, different distributions and
different modifications.
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- Collagen type 1: the strongest type of collagen, most common. Found
in skin, tendons, capsule, dentin, cementum and bone.
- Collagen type 3: Reticuloendothelial system, reticular lamina of
basement membrane.
- Collagen type 4: basal lamina.

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How the collagen is synthesized?
- Fibroblast makes the extracellular matrix; DNA transcription for
collagen mRNA in nucleus, mRNA is translated in the rough
endoplasmic reticulum (a glycosylation step + hydroxylation-the
addition of a hydroxyl group-)
- Then it gets modified in the Golgi apparatus (addition of sugar-
glycosylation), then it gets exported from the cell by exocytosis, the
product is called Procollagen (not the final form of collagen, pro
means before).

- Procollagen is made up of triple alpha helical chains + nonhelical

parts on the edges

- There is a certain enzyme in the extracellular matrix that cuts these

edges, after cutting the edges it's called Tropocollagen.

- The Tropocollagens align next to each other and above each other to
form Collagen Fibril "smaller than the fiber".

- Collagen Fibrils aggregate to form Collagen Fiber.

- Collagen Fibers aggregate to form Collagen Bundle.

- Only collagen type 1 can form collagen bundles, while collagen type
3 forms fibers (thin fibers), collagen type 2 forms fibrils, collagen
type 4 in basal lamina forms sheets.

- In collagen type one each third amino acid is glycine, also each helix
is rich in proline and lysine.
- The process of synthesizing collagen is a very long process and has
many steps; any defect in any step will result in defective collagen
(result in diseases).
- For example, Hydroxylation step needs Vitamin C.
- Our body does not synthesize vitamin C, the source of this vitamin is
the diet.
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Clinical applications:
✓ At the surgical incision site, the site is filled with collagen fibers
synthesized by fibroblasts (the fibrocytes in the connective tissue are
activated due to injury (became fibroblasts)). This is called scar
formation, and it’s part of the normal healing process (formation of
pink line). But in certain people, there will be excessive formation of
collagen "the fibroblasts form high amount of collagen”, then the
incision site will appear larger in size, elevated from the surface and
with very ugly appearance. This is called Keloid. Keloid is common
in Africans.

✓ Scurvy : deficiency in vitamin C, which is very important in the

hydroxylation step. This result in defective collagen, the patient has
hemorrhage (bleeding) in a lot of areas. The patient is anemic and
the gums are bleeding.

✓ The third type is also caused by defective collagen; the joints are
hyperflexible and hypermobile. Ehlers–Danlos syndrome

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