Lecture 10 - Cartilage Structure And Composition Flashcards

1
Q

What stabilises collagen?

A

Covalent cross-links

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2
Q

How is a cross link formed?

A

Formed by two lysine residues which are joined together to form an aldol cross link

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3
Q

What is ehlers danlos - type 5?

A

It is a syndrome where collagen should be strengthen but instead you get stretchiness

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4
Q

What is SCAD?

A

Spontaneous coronary artery dissection - which means that the coronary artery splits as the collagen is ineffective in holding the vessel together and results in a heart attack

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5
Q

What are heterofibrils collagens used in adult articular cartilage?

A

Type 9 and type 11, type 2 is the main collagen type in adults

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6
Q

What can mutations in collagens 9 and 11 result in?

A

Chondrodysplasia syndromes

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7
Q

What collagen can be seen in cartilage?

A

Type 3 - it seems to get more prevalent in oesteroarthitus

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8
Q

What is noticeable in the histology with someone who has osteoarthritis (OA)?

A

There are fewer cells - the cells are dividing but there are spaces where they are no cells

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9
Q

What makes a proteoglycan?

A

Protein and glycan (polysaccharide)

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10
Q

Proteoglycans are a special class of …..

A

Glycoproteins

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11
Q

What are proteoglycans normally low and high in?

A

Low in proteins and high in polysaccharide chains

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12
Q

What type of specialised polysaccharide chains are attached to proteoglycans?

A

Glycoaminoglycans (GAG chains) which are joined by their reducing terminal sugar residues to the protein

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13
Q

What do proteoglycans give?

A

‘Bottle-brush’ confirmation (how it looks)

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14
Q

What is attached to the central protein core of a proteoglycan?

A

GAG chains - which forms the bottle brush Structure

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15
Q

Are GAGs highly negatively charged or positively charged?

A

Highly negatively charged with lots of esters attached to

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16
Q

What is an aggrecan?

A

An aggrecan is a cartilage proteoglycan (all glycoproteins end in can)

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17
Q

Why is cartilage proteoglycan called an aggrecan?

A

Because it aggregates which means it can form gel like properties

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18
Q

How can aggrecans be measured?

A

By finding an increase in viscosity

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19
Q

What is the structure of aggrecans?

A

3 globular domains with a protein core, an N terminal G1, two types of GAGs and keratan sulphate chains (KS) and Chondroitin chains (Cs)

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20
Q

What globular chain is very important in aggregation?

A

G1 which is also the N terminal

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21
Q

What are the two ways the Cs chains can be arranged?

A

Regulatory spaced (Gs1) and in clusters (Gs2)

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22
Q

What sulphate chains are shorter, keratan or chondroitin?

A

Keratan are shorter

23
Q

What is the structure for keratan?

A

A repeating disaccharide structure, for every disaccharide you get more negative charge

24
Q

What is different for the structure of Keratan and the structure for chondroitin?

A

Chondroitin has a Glucuronic acid (glucosamine) and keratan has galactose (galactosamine)

25
Q

What is imporant when you stop growing?

A

Need to stabilise the matrix, stabilise the cartilage so C-6 sulphate is important as well as Keratan

26
Q

What is different to babies and adult cartilage?

A

The cartilage in babies need to be remodelled, as babies grow therefore cartilage needs to be broken down or calcified to be converted into bone

27
Q

What could happen when you damage cartilage?

A

The body could use the wrong proteoglycans - could used foetal proteoglycans

28
Q

What happens after every repeating disaccharide in chondroitin cartilage?

A

Get two negative charges

29
Q

What specific linkage so GAGs have?

A

Glycosidic linkage (O)

30
Q

What does the level of glycosylation depend on?

A

The age of the tissue

31
Q

What does aggrecan glycosylation contain?

A

100 CS chains, 30-60Ks, CS-1 evenly distributed and CS-2 clusters with a MW of 2 million

32
Q

How many repeating disaccharide units does aggrecan glycosylation have in Cs chains?

A

40 repeating disaccharides with 80 negative charged per chain

33
Q

What is the aggrecan glycosylation like Ks chains?

A

8000Mw, 8-16 repeating chains with 8-16 negative charges over chain

34
Q

What is the aggrecan protein core like?

A

G1 - is the N terminal globular region which interacts with another glycosaminoglycan (HYALURONAN)

35
Q

Is hyaluronan sulphated?

A

NO

36
Q

What is the size of the proteoglycan aggregate dependent on?

A

How long the hyaluronic acid is

37
Q

What are proteoglycans in the extracellular matrix present as?

A

Multi molecular aggregates

38
Q

What do aggregates consist of?

A

Many proteoglycan monomers bound to a single molecule of hyaluronan by an IONIC interaction

39
Q

What does the ionic interaction do in proteoglycan aggregates?

A

It is stabilised by 2 link proteins with MW of 40,000 and 50,000

40
Q

How large can aggregates be?

A

Can have a MW weight up to 1million

41
Q

What is hyaluronan important in?

A

In developing the hindlimb

42
Q

HAS =

A

Hyaluronic acid synthetase (HAS2) - important in developing the hindlimb

43
Q

What happens if you delete HAS2 genes?

A

Results in much shorter limbs and the joint is not properly formed

44
Q

What is the development of the joint and limbs like?

A

Starts off as cartilage and as the joints develop it gets calcified and becomes bone

45
Q

What is the structure of link proteins?

A

Has immunoglobulin like folds - two other globulin domains which are tandem repeats

46
Q

What is the structure of G1?

A

It has a similar structure to link proteins, it has N linked sugars which would be linked to asparagine

47
Q

What can G1 interact with?

A

Hyaluronic acid, it has one A and two B domains, the B domains are involved in binding to hyaluronic acid, A domains bind to each other binding to the link proteins

48
Q

How many sugars of hyaluronic acid is important for binding?

A

It needs 10 sugars to = 5nm

49
Q

How big are the globular domains?

A

3x3nm which is big enough to get the 10 sugars of hyaluronic acid

50
Q

What is involved in maintain hydrophobic amino acid?

A

Tryptophan and is maintains the globular conformation of G1

51
Q

What is necessary to get a reaction between the G1 region and reaping unit of hyaluronan?

A

3-Nacetyl groups

52
Q

What is the interaction between proteoglycan and hyaluronan like under physiological conditions?

A

An equilibrium exists between PGS, HA and the complex, equilibrium will shift in favour of the complex group, there is no equilibrium once you add link proteins

53
Q

What has been found in recent studies to do with HAS2?

A

On cartilage specific HAS2 knockout mice - in the absence of HAS2 gene expression it resulted in severely abnormal Skeleton and perinatal death - Roughley P.J (2006)