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Biomed year 2 sem 1 > BMS2002 - extracellular matrix > Flashcards

BMS2002 - extracellular matrix Flashcards

1
Q

basal lamina

A

thin layer/mat of connective tissue comprised of mostly ECM that cells attach to
- essential for maintaining epithelial tissues

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2
Q

apical =

A

cells touching the free surface

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3
Q

basal =

A

cells touching the basal lamina

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4
Q

Adherens junction

A

cell junction where cadherins connect to actin in cytoskeleton

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5
Q

cadherin

A

calcium ion dependent
homophilic binding

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6
Q

cadherin domains

A
  • 5 copies of EC domain separated by flexible hinge regions
  • calcium binding prevents flexing -> promotes binding to another cadherin
  • IC domains interact with actin via catenin and adapter proteins e.g. vinculin
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7
Q

Desmosomes

A

cell junction that uses cadherins that connect to intermediate filaments in cytoskeletal filaments

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8
Q

tight junction

A

epithelial sheet seals two neightboring cells together
- prevents leakage of EC molecules between them
- helps polarize cells
- apical transporters allow selective transport across epithelia

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9
Q

gap junction

A

forms small channels from connexins and innexins
- allow small, water-soluble molecules to pass cell-cell

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10
Q

actin-linked cell matrix junction

A

anchors actin filaments in a cell to ECM

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11
Q

hemidesmosome

A

anchors intermediate filaments in a cell to ECM

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12
Q

what is basal lamina composed of?

A

laminin, collagen type IV, XVIII, nidogen, perlecan, fibronectin

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13
Q

indigenous cells in connective tissue

A

primitive mesenchymal cells
fibroblast
specialised cells

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14
Q

immigrant cells in connective tissue

A

immune cells

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15
Q

composition of connective tissue ECM

A
  1. GAGs (glycoaminoglycans)
  2. fibrous proteins - collagen family
  3. glycoproteins e.g. elastin, fibronectin
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16
Q

GAGs

A

Glycoaminoglycans
- large, highly charged polysaccharides that bind lots of water
- v. anionic
- consist of repeated sulphated disaccharide units
- bind proteoglycans to forms complexes (e.g. aggrecan) that can self-aggregate

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17
Q

collagen

A
  • long, stiff, triple strand helical structure
  • provides tensile strength
  • 3 alpha polypeptides form a coil -> can self aggregate into fibrils and fibres once outside the cell
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18
Q

procollagen

A

prevents collagen aggregation while inside cells

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19
Q

Elastins

A

provide elasticity to connective tissues
- similar structure to collagen
- dominant component of ECM in arteries

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20
Q

Fibronectins

A
  • bind other matrix/cell membrane proteins
  • organise matric and provide cell-matrix link
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21
Q

Integrins

A

key receptors that allow ECM to interact with cytoskeleton
- provides strength
- used to pull some components through the ECM (need to make and break connections)

22
Q

Talin

A

important integrins adapter molecules

23
Q

Activating integrins (inteacellular signalling)

A

thrombonin binds receptor -> Rap1 converts GDP to GTP -> inactive integrin + RIAM + inactive talin + kindlin -> active integrin -> viniculin allows integrin to connect to actin -> provides physical link to cytoskeleton

24
Q

too much matrix synthesis, not enough breakdown ->

A

alteration of function
- tissue scarring, fibrosis, cancer

25
Q

too much matrix breakdown, not enough synthesis ->

A

loss of function
- developmental/induced deficiencies
- arthritis
- metastasis

26
Q

what do metalloproteinases need to be active?

A

Zinc, Zn2+

27
Q

3 families of metalloproteinases?

A
  1. MMP - matrix metalloproteinases e.g. collaginases
  2. ADAM - a disentegrin-like metalloproteinases
  3. ADAMTS - ADAM with thrombospondin motifs (involved in ECM catabolism)
28
Q

metalloproteinases

A

key modifiers mediating catabolism of ECM components
- release/activation of growth factors, hormones, cytokines
- anchored in ECM

29
Q

metalloproteinase characteristics

A
  • Zn2+ binding domain
  • secretion into ECM as pro-enzymes
  • activated by removal of pro-region by proteinases
30
Q

metalloproteinase inhibitors

A
  • A2 macroglobulins
  • TIMPs - tissue inhibitors of metalloproteinases: slot into catalytic domains
31
Q

ECM remodelling (homeostasis)

A

loading stress -> fragments ECM components -> fragments stimulate ECM synthesis -> restores healthy matrix

32
Q

ECM remodelling is essential during

A
  1. embryonic development
  2. wound healing
  3. prevention of tumor development - tumour cells held up in matrix -> can’t grown and develop
33
Q

3 main types of cartilage

A
  1. Hyaline (articular)
  2. fibro
  3. elastic
34
Q

components of Hyaline cartilage

A
  • defined by the presence of indigenous chondrocytes
  • type 2 collagen and aggrecan -> strength and support
35
Q

proteoglycans

A
  • highly charged: can associate lots of water -> hydrated gel
  • provides resistance to compression - swelling
  • strength and support
36
Q

Adult stem cells only contain one cell type:

A

chondrocytes
- secrete components that establish cartilage

37
Q

chondrocytes differentiate from…

A

mesenchymas stem cells (MSC) during embryonic development

38
Q

key signal for cartilage -> bone

A

Sox9

39
Q

how does bone grow from cartillage

A

from the centre, forcing caritlage towards the end - inside out

40
Q

control of PTHrP

A

PTHrP = key skeletal morphogen (hedgehog responsive gene)
- IHH and PTHrP in positive feedback loop that maintain spatial chondrocyte proliferation
Hedgehog signalling

41
Q

formation of long bones

A

cartilage is catabolized
osteoid ECM becomes calcified -> traps osteoblasts
from inside out and then from each end (distal/proximal epiphys)

42
Q

osteoblast ->

A

osteocyte -> becomes trapped in osteoid
responsible for bone homeostasis

43
Q

osteoid

A

bone ECM

44
Q

osteoclasts

A

break down newly formed bone -> cavity for bone marrow

45
Q

IHH/PTHrP feedback in long bone formation

A

PTHrP maintains chondrocyte poliferation and prevents their terminal differentiation
As proliferating cells move further from central cells, they recieve less PTHrp
This also reduced IHH -> make less PTHrP -> become more osteoblast-like
-> contributes to the ossification process

46
Q

cartilage model

A

embryonic bones - replaced by bone during development

47
Q

Key components broken down in OA

A

Aggrecan and collagen
- more dependent on collagen cleavage than aggregan destruction

48
Q

GDF5

A

gene involved in OA
- growth factor member of TGF-b fam
- important in ECM homesotasis

49
Q

RUNX2

A

gene involved in OA
- master transcription factor responsible for driving endochondrial ossification (MMP-13 expression)

50
Q

PTHLH

A

gene involed in OA
- encodes PTHrP chondrocyte growth factor driven by IHH secretion

51
Q

SMAD3

A

gene involved in OA
- intracellular signalling protein involved in TGF-b production
- induces ECM synthesis, reduces MMP expression

52
Q

Rheumatoid arthritis is characterised by

A

inflammation in the synovium

Biomed year 2 sem 1 (7 decks)

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