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Infection, immunity and repair > Mechanisms of ECM formation > Flashcards

Mechanisms of ECM formation Flashcards

1
Q

What is remodelling?

A

Reorganization or reinovation of existing tissues - causes structural changes in fully differentiated tissues

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2
Q

What happens during tissue repair?

A

Remodelling replaces the temporary repair structure with a functional new tissue

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3
Q

What can remodelling do to properties of tissues?

A

Can change the characteristics of a tissue

Result in dynamic equilibrium of a tissue

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4
Q

What is an example of a tissue in which remodelling is essential for the equilibrium of the tissue?

A

Bone remodelling

Bone tissue is constantly remodelled throughout life and renewed during changes in excercise and growth

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5
Q

What is an example in which remodelling leads to pathology?

A

Vascular remodelling causes blood vessels to get thicker and less functional in hypertension

Sometimes causes loss of function

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6
Q

What is the key aspect of remodelling?

A

Restoring function

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7
Q

What are the two things you have to restore in order to restore function of a tissue?

A

Tissue composition - same cells and matrix components

Tissue structure - cell and matrix arrangement as well as biomechanical properties

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8
Q

What activates tissue remodelling?

A

Normal physiology and growth - bones need remodelling to maintain homeostasis of the bone -> bone has to grow with the body

Exercise - the more you exercise the muscle, bone becomes stronger

Repair after injury

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9
Q

What are the two types of injury that can occur to the bone?

A

Mechanical disruptions - fracture

Disease related - inflammation and bacterial infection

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10
Q

What balance does bone remodelling represent?

A

Balance between:

Bone resorption

Bone ossification

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11
Q

What cells remodel tissues?

A

Inflammatory cells - secrete proteases that degrade matrix

Fibroblasts - stimulated by cytokies and growth factors

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12
Q

How do fibroblasts remodel the matrix?

A

Actively remodels the matrix by:

Pulling on it

Secreting proteases

Synthesizing new matrix

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13
Q

ECM can be made by inflammatory cells

TRUE or FALSE

A

FALSE

Fibroblasts form ECM

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14
Q

How many nuclei do osteoclasts have?

A

Multinucleated

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15
Q

How many nuclei do osteoblasts have?

A

Mononucleated

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16
Q

What is the role of osteoclasts?

A

Destroy the bone matrix

Clean up the wound and destroy unhealthy tissue

So osteoblasts can form new healthy tissue

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17
Q

What is the role of osteoblasts?

A

Synthesize and mineralise new bone matrix

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18
Q

Steps of bone remodelling following injury

A

Input from outside triggers remodeling

Osteoclasts are recruited

Move through lining of bone cells

Osteoclasts digests the tissues

Osteoblasts move into hole of digested tissue and fill it with temporary tissue

Further matrix synthesis and mineralisation creates new tissue

Bone formation finishes

Osteoblasts will enter quiescent state and form lining bone cells

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19
Q

Which cells are important in the wound healing process?

A

Macrophages and fibroblasts - release GF and cytokines

Fibrin clot - clot skin temporarily and recruits more inflammatory cells via release of cofactors

Fibrin - contains immune complexes that release GF

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20
Q

What is the most significant GF in wound healing?

A

TGFb

Activate fibroblasts to contract and form new ECM

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21
Q

What are myofibroblasts?

A

Muscle-y fibroblasts that develop during the conctraction phase

22
Q

What are the 4 stages of healing?

A

Hemostasis - fibrin clots and blocks the wound

Inflammatory phase - cytokines and GF are released by WBC due to damage

Proliferative phase - recruitment of fibroblasts and WBC

Wound contraction and matrix remodelling - get rid of replacement tissue. Myofibroblasts contract the tissue actively and secrete more ECM

23
Q

Which cells contract the damaged tissues?

A

Myofibroblasts

24
Q

How are myofibroblasts formed?

A

Fibroblast differentiate into myofibroblasts under the control fo TGFb

25
Q

Which cells secrete TGFb?

A

Immune complexes

26
Q

Describe the structure of myofibroblasts

A

Made of bundles of filaments of specific isoforms of actin

a-SMA = alpha smooth muscle actin

27
Q

What is the role of myofibroblasts?

A

Contractile cytoskeleton

Grab the matrix and mechanically move it close to the wound site

Also secrete collagen and fibronectin matrix

28
Q

Which matrix components are important in remodelling?

A

Collagens

Elastins

GAGs

Proteoglycans

Fibronectin

Laminin

29
Q

What is the most abundant protein in the body?

A

Collagen

30
Q

What are the 4 major types of collagen?

A

Collagen I - all connective tissue

Collagen II - cartilage

Collagen III - cartilage

Collagen IV - basement membrane

31
Q

What is the role of elastins?

A

Elasticity

Load bearing rebound

32
Q

What is the role of GAGs?

A

Interact with collagen and elastin

33
Q

What is the structure of PGs?

A

GAGs on protein core

34
Q

What is the role of PGs?

A

Highly hydrated - osmotic gradient created by GAGs

Serves as lubricants or cushions

35
Q

What is Fibronectin?

A

Multi adhesive protein binding colllagen

36
Q

What is Laminin?

A

Multi adhesive protein fonu in basal lamina

37
Q

What are types of enzymes that degrade ECM?

A

MMPs

Cathepsin K

ADAMT

38
Q

What are MMPs?

A

Matrix metalloproteinases

Main family that degrade components of the matrix

Secreted by inflammatory cells, fibroblasts and specialised cells

39
Q

Which specialised cells secrete MMPs?

A

Chondrocytes

Osteoclasts

40
Q

What are TIMPs?

A

Inhibitors of MMPs

41
Q

What does TIMP/MMP ration determine?

A

Whether tissue will be degraded or remodelled

42
Q

What does Cathepsin K degrade?

A

Bone elastin and collagen

43
Q

What does ADAMT degrade?

A

Cartilage matrix - aggrecan units

44
Q

What is the biological consequence of matrix degradation?

A

Release of matrix-bound GF and peptides

Nature of factors released can determine whether tissue is remodelled or broken down

45
Q

What is mechanosensing?

A

Link between mechanical tension and matrix remodelling

46
Q

How do cells sense tension?

A

Integrin links ECM to cell cytoskeleton

Forces are tranmitted from outside the cell to the inside

Integrin relays mechanical stress and relays the information to the actin or intermediate filament cytoskeleton

47
Q

What are cadherins?

A

Cell surface receptors that permit cell to attach to each other

So the forces can be transmitted from one cell to another

48
Q

What is the difference between integrins and cadherins?

A

Integrins relays stress from outside to inside cytoskeleton

Cadherins relays stress from cell to cell

49
Q

How is mechanical stress converted into a signal the cell understands?

A

Mechanical signals is picked up by integrins/ cadherins

Converted to biochemical signals inside the cells

This triggers signal transduction cascades that lead to gene expression

Turn cellls more contractile and start formation of cytokines

Also determines matrix components

50
Q

Examples of pathologies that arise if remodelling goes wrong

A

Tissue lose function if remodelling goes wrong - too stiff/ soft

Osteoporosis - too much degradation

Osteoarthritis

Hypertension

Paget’s bone disease - bone overgrowth

Infection, immunity and repair (52 decks)

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