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Physiology & Science: Musculoskeletal > Fibrous extracellular matrix proteins > Flashcards

Fibrous extracellular matrix proteins Flashcards

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1
Q

What are examples of connective tissue?

A
  • Blood
  • Bone
  • Tendon
  • Skin
  • Ligament
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2
Q

What pathological conditions are associated with abnormalities of the extracellular matrix?

A
  • Arthritis
  • Osteoporosis
  • Cancer
  • Diabetes
  • Ageing
  • Scars/fibrosis
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3
Q

What are 2 important fibrous proteins that make up the extracellular matrix?

A

Collagen + elastin

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4
Q

How are the collagen fibrils arranged in:

  • tendons/ligaments
  • bone
  • cartilage
A
  • tendons/lig - parallel bundles
  • bone - spirals
  • cartilage - meshwork
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5
Q

How many alpha chains are there in collagen forming the helix?

A

3 a chains - triple helix

Triple helices cross-link to form a FIBRIL

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6
Q

Each a chain is typically 3 amino acid repeats, what are they?

A

Glycine - proline - hydoxyproline

(Glycine ALWAYS as it acts as the glue, the other two are usual but not always)

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7
Q

Describe the pathway for synthesis of fibril-forming collagens

A
  • Pro-alpha chains modified in ER
  • Triple helix formed -> procollagen
  • (extracellular) Procollagen secreted
  • Propeptides cleaved -> collagen
  • Striated + strength
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8
Q

How many known alpha chains are there for collagen structure?

A

25 known a-chains, >10,000 possibilities but only 20 types of collagen molecules found

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9
Q

What are the 3 most important collagen types?

A

I, II, III

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10
Q

Where is collagen type I found?

A

Bone

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11
Q

Where is collagen type III found?

A

Woven bone (not as strong as type I)

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12
Q

Where is collagen type II found?

A

Hyaline cartilage

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13
Q

What is the difference between a collagen fibril and fibre?

A
  • Collagen molecule = 3 alpha chains forming a triple helix
  • Collagen fibril = lots of overlapping molecules
  • Collagen fibre = lots and lots of fibrils
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14
Q

Collagen types I and III are fibrillar collagens. There is another type called sheet-like collagens, how are they different + give an example?

A
  • Type IV - in skin
  • Lack regular glycine -> loose helix -> inc flexibility
  • -> Sensitivity to digestion with proteases (so easily destroyed)
  • Terminal peptides not cleaved
  • Assemble head-to-head, form a sheet
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15
Q

What substances help to increase synthesis of extracellular matrix?

A
  • TGF-beta (transforming growth factor-beta)
  • PDGF (platelet derived growth factor)
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16
Q

What decreases synthesis of extracellular matrix?

A
  • Glucocorticoids
  • Age
17
Q

What substances increase degradation of extracellular matrix?

A

MMPs (matrix metalloproteinases)

18
Q

What substances decrease degradation of extracellular matrix?

A

TIMPs - tissue inhibitors of MMPS

19
Q

What does collagenase (MMP1) destroy?

A

Native fibrillar collagens (type I, III etc)

20
Q

What does gelatinase (MMP2/9) destroy?

A
  • Denatured collagens
  • Elastin
  • Type IV (sheet like) collagen
21
Q

What does stromelysin (MMP3) destroy?

A
  • Type IV collagen
  • Fibronectin
  • Proteoglycans
22
Q

Which proteolytic enzyme is involved in bone resorption?

A

Cathepsin K

23
Q

What happens in scurvy?

A
  • Loss of collagen
  • Loss of glycine -> forms sheet-like collagen instead
  • peridontal ligament (in teeth) broken down -> teeth fall out
24
Q

There is a type 1 collagen mutation in osteogenesis imperfecta. What is glycine replaced with?

A

Cysteine -> disrupts alpha helix

25
Q

What happens in achondrogenesis?

A

Type II collagen mutation - severe effects on development of cartilage and bone

26
Q

What happens in Ehlers-danlos syndromes?

A

Type III or V collagent mutation - joint hyper mobility, skin extensibility, rupture of blood vessels

27
Q

Elastin core is covered by sheath of microfibrils. The microfibrils are composed of which glycoprotein namely?

A

Fibrillin

The microfibrils are essential for integrity of elastic fibres

28
Q

Does elastase increase or decrease synthesis of elastin? What inhibits elastase?

A

Decrease - it is inhibited by a1-anti-trypsin

29
Q

What happens to elastin synthesis in hypertension?

A

Increased synthesis and deposition of elastin and collagen in vessel walls - they become thickened and diameter becomes reduced.

The turnover of elastin + collagen is slow, so difficult to treat.

30
Q

What happens to elastin in pulmonary emphysema?

A

Loss of elastin = reduced elasticity of the lungs, sometimes due to deficiency of a1-anti-trypsin - needed to inhibit elastase.

So too much elastase = excessive degradation.

31
Q

What is cutis laxa?

A

Loss of elastin - makes skin appear wrinkly

32
Q

What is Marfan syndrome?

A

Mutation in fibrillin gene -> arachnodactyly, pectus excavatum, dilation of aorta

Physiology & Science: Musculoskeletal (17 decks)

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