Composition and structure of connective tissue

Question 1

Give 3 examples of functions of connective tissue?

Answer 1

Mechanical support

Assist movement

Site of immune response

Question 2

Do connective tissues contain neurovascular structures?

Answer 2

Yes

Question 3

What are the 3 main components of connective tissue?

Answer 3

Cells

Structural components (in ECM)

Matricellular proteins (in ECM)

Question 4

What is the function of cells in connective tissue, and give 3 examples of body structures that contain connective tissue and the associated cells?

Answer 4

Cells synthesise and breakdown connective tissue

Fibroblasts in skin and tendon ligaments

Chondrocytes in cartilage

Osteocytes, osteoblasts, osteoclasts in bone

Question 5

What is the main function of structural components in connective tissue?

Answer 5

Provide mechanical properties by providing ground substance

Question 6

What is ground substance, that composes structural components of connective tissue?

Answer 6

Amorphous/shapeless gelatinous material that contains all ECM components except from fibrous materials

Question 7

What 3 substances make up the ground substance in the structural components of connective tissue?

Answer 7

proteoglycan predominantly, elastic and collagen fibres

Question 8

Describe the structure of a proteoglycan?

Answer 8

Protein core coated by sugar-based polymers called glycosaminoglycans/GAGs/glycans

Different kinds of glycans which are built from different building blocks

Question 9

Give 4 examples of properties of proteoglycans?

Answer 9

size variation ranges from 40dKa to over 100dKa

hydrophilic so allow water to be held in tissues

viscoelastic

interaction with cells, collagen and cytokines

Question 10

What is aggrecan, and how does it form aggregate?

Answer 10

Aggrecans are proteoglycans that cluster with hyaluronan and link proteins to form a huge multimeric (protein composed of subunits) aggregate

Aggregate is a ball-shaped structures that give cartilage resistance to compression in cartilage

Question 11

What is the function of link proteins in aggregate?

Answer 11

Link proteins stabilise binding of aggrecans to hyaluronan backbone

Question 12

What structure coating aggregate makes it hydrophilic, and what property does this give the connective tissue overall?

Answer 12

Hydrophilic sulfated chondroitin-keratin sulphate complex chains of aggregates draw water into tissue which allows resistance to compression

Question 13

In OA, how are aggregates and type 2 collagen fibres affected?

Answer 13

In OA, aggrecan and type II collagen are degraded by proteolytic enzymes which impairs mechanical properties of cartilage, causing joint pain

Question 14

Do matricellular proteins have regulatory or structural roles?

Answer 14

Regulatory

Question 15

In elastic fibres, what is the diameter of the microfibrils that compose them?

Answer 15

10nm

Question 16

What 4 body structures contain elastic fibres so that they can stretch?

Answer 16

blood vessel walls, alveoli, bladder, tendons

Question 17

What do elastic fibres target and activate?

Answer 17

Growth factors, especially TGF-beta

Question 18

What 4 proteins compose elastic fibres?

Answer 18

elastin

fibrillin 1,2,3 proteins

fibulin 4,5 proteins

matrix-associated glycoproteins

Question 19

Describe the composition and arrangement of elastic fibres in tendons?

Answer 19

In tendons, elastic fibres composed by long microfibrils and sit between collagen fibre bundles

Question 20

What is the main matricellular protein and structural component of connective tissue?

Answer 20

Type 1,2,3 collagen fibres

Question 21

How many types of collagen are there, and how many genes are these expressed by?

Answer 21

27 collagens that are expressed by 42 genes

Question 22

What is each collagen molecule in a collagen fibril composed of, and how many genes are expressed to produce these?

Answer 22

Collagen fibrils are composed of many collagen molecules, with each molecule consisting of triple helix alpha polypeptide chains

each chain is a single gene product

Question 23

What is the amino acid sequence of an alpha polypeptide chain which makes up collagen fibrils?

Answer 23

Glycine-X-Y repeats, where X is usually proline and Y is usually hydroxyproline (unusual AA that is mostly found in collagen)

Question 24

What part of the amino acid sequence of alpha polypeptide chains allows them to intertwine and form a triple helix alpha polypeptide molecule?

Answer 24

Glycine is every 3rd residue in the amino acid sequence

Question 25

What 2 properties do proline and hydroxyproline give collagen?

Answer 25

Rigidity, stability

Question 26

Describe the turnover rate of collagen fibres?

Answer 26

Very slow turnover rate, so collagen is very stable

Question 27

What percentage of the whole-body protein content is made up by collagen fibres?

Answer 27

12-17%

Question 28

What is a homotrimer collagen and give one example?

Answer 28

Protein composed of 3 identical alpha polypeptide chains eg. Type 2 collagen

Question 29

What is a heterotrimer collagen and give one example

Answer 29

Protein composed of 2 or more different alpha polypeptide chains eg. Type 1 collagen in skin and bone has 2 identical alpha chains and 1 different alpha chain

Question 30

In collagen fibril synthesis, what occurs after alpha polypeptide chain translation?

Answer 30

Post-translational modification at RER of alpha polypeptide chain: proline and lysine hydroxylation (vitamin C/ascorbate is cofactor) hydroxylysine glycosylation

Question 31

In collagen fibril synthesis, after the 3 alpha polypeptide chains have been modified how do they assemble into the triple helix alpha polypeptide molecules, and what is the name of this molecule?

Answer 31

3 modified alpha polypeptide chains form disulfide bonds between them to intertwine tightly and produce triple helix alpha polypeptide molecule which is called procollagen

Question 32

In collagen synthesis, what happens to procollagen after it is produced in the cell?

Answer 32

Procollagen secreted from cell by exocytosis and enters ECM

Question 33

In collagen fibril synthesis, how is procollagen converted into tropocollagen?

Answer 33

In ECM, N and C proteinases cleave N and C propeptides from procollagen, converting it to tropocollagen

Question 34

In collagen fibril synthesis, how do tropocollagen molecules from a collagen fibril, and what enzyme catalyses this step?

Answer 34

Tropocollagen molecules assemble into collagen fibrils, then lysyl oxidase forms covalent cross-linkages between the molecules

Question 35

How can vitamin C deficiency affect the strength of collagen fibrils, and what is the resulting condition?

Answer 35

Vitamin C deficiency reduces hydroxylation of proline and lysine, which weakens triple helix structure of procollagen, overall weaker collagen fibrils are formed and this presents as scurvy

Question 36

Give 5 symptoms of scurvy?

Answer 36

Gum bleeding, teeth loss, skin lesions and bruising, joint pain and weakness, poor wound healing

Question 37

Do all connective tissues have the same composition and organisation of collagen?

Answer 37

Different types of connective tissues have varying compositions and organisations of collagen

Question 38

What is the primary protein component in bone, and how is it organised?

Answer 38

Primary protein component is type 1 collagen fibres which are arranged into concentric circular structures called lamellae

Question 39

In tendons, how does collagen provide high tensile strength?

Answer 39

Parallel type 1 collagen fibre bundles provide tensile strength

Question 40

In enthesis, do the proportions of collagen remain constant throughout its length?

Answer 40

No, enthesis structure varies along it length due to different collagen proportions

Question 41

Why is the enthesis a common site of tendon pathology, and give 2 examples?

Answer 41

Mechanical stress is concentrated here, so microdamage and overuse injuries often occur

Question 42

Give 5 examples of tendinopathy changes to collagen proportions and organisation?

Answer 42

Disorganised collagen fibrils reduced fibril diameter increased collagen turnover leads to higher proportion of type 3 collagen fibres neurovascular infiltration which causes pain failure to repair

Question 43

In skin and blood vessels, what type of collagen forms the collagen fibrils?

Answer 43

Mixed fibrils formed from type 1,3 collagen

Question 44

What kind of deficiencies can cause conditions with fragile skin and blood vessels?

Answer 44

Fragility occurs due to impaired collagen fibril formation from deficiencies in type 3 collagen (expressed by COL3A1 gene) which can lead to conditions such as Ehlers Danlos syndrome type IV

Question 45

What percentages of types 1 and 3 collagen make up skin and blood vessels?

Answer 45

~60% type 1 collagen ~30% type 3 collagen