LOCO Revision1 Flashcards

1
Q

Which cell makes type 1 collagen?

osteoclasts
osteoblasts
osteocyte
osteoprogenitor

A

Which cell makes type 1 collagen?

osteoclasts
osteoblasts
osteocyte
osteoprogenitor

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2
Q

Name two places that may find red bone in an adult [2]

A

spongy / trabeculae bones of vertebrae, ribs, sternum, cranium and epiphyses of long bones

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3
Q

Describe action of increased PTH [3]

A

Low Ca2+ levels stimulates PTH secretion

PTH promotes:
* Ca2+ reabsorption from kidney and PO4 excretion at the kidney

  • Osteoblasts have receptor for PTH, osteoblasts produce RANKL, osteoclasts and their precursors have RANK receptor; increases number and activity of osteoclasts
  • Synthesis of 1,25-dihydroxyvitamin D (1,25 (OH)2 vitamin D3)
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4
Q

Which receptor does FGF23 bind to? [1]

What is the effect of FGF23 activation? [3]

A

FGF23 produced by osteoclasts / blasts, targets the kidney:

FGF23 binds to Klotho

Action:
* Causes reductions in serum phosphate and 1,25(OH)2D levels
* Reduces PTH secretion

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5
Q

Name 3 pro-inflammatory RANKL inducers [3]

Name 1 RANKL inhibitor [1]

A

Inducers
TNF-a
IL-1
Prostaglandin E2

Inhibitors
Oestrogen

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6
Q

FGF23 effect on PTH? [1]

A

Switches off PTH

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7
Q

Where is calcitonin produced? [1]

What triggers calcitonin release? [1]

What is the effect of calcitonin? [1]

A

Calcitonin produced in thyroid gland

Produced when Ca2+ leves rise

Calcitonin reduces Ca2+ levels

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8
Q

Describe the physiological effects of calcitonin [3]

A
  • inhibits osteoclast differentiation and activity
  • increases Ca2+ excretion from kidney
  • Inhibits Ca2+ absorption by intestines
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9
Q

Describe effect of oestrogen at the:

Gut [1]
Bone [1]

A

Gut - increased Ca2+ absorption
Bone - decreased re-absorption (inhibit osteoclasts)

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10
Q

Describe the effect of adding progesterone ceram to osteoporosis therapy [1]

A

increases bone density by around 10% in 1st 6 months to rate of 3-5% annually stabilises at levels of 35 year old

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11
Q

Describe the action of FSH on osteoclasts [1]

Describe the action of FSH on IL-1. TNF and IL6 [1]

A

Direct action on osteoclasts upregulates RANK

Indirect action on monocytes to secrete IL1, TNF and IL6

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12
Q

Ca2+ homeostasis

Describe effect of glucocorticoids at the:

Gut [1]
Bone [1]

A

Gut - decrease Ca2+ absorption

Bone - increased re-absorption/decreased formation

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13
Q

Describe the effect of 1,25(OH)2D acting on vitamin D receptor:

  • During normal levels of 1,25(OH)2D
  • During elevated levels of 1,25(OH)2D
A

Normal levels of 1,25(OH)2D act via the VDR (Vitamin D Receptor) in mature osteoblasts to decrease the ratio of RANKL/OPG and reduce osteoclastic bone resorption. As well, 1,25(OH)2D action via the VDR in mature osteoblasts increases the bone formation rate (BFR).

Increased levels of 1,25(OH)2D acting via the VDR in less mature osteoblasts may increase RANKL/OPG, stimulate osteoclastic bone resorption, and reduce trabecular bone
The action of high levels of 1,25(OH)2D in mature osteoblasts and osteocytes can increase local and systemic inhibitors of osseous mineralization and decrease mineralization of bone leading to osteomalacia

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14
Q

Prolonged corticosteroid treatment leads to which disease? [1]

A

osteoporosis

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15
Q

Describe the role of EphrinB2 anad ephB4 [2]

On which cells are each located? [2]

A

EphrinB2 produced by osteoclast

EphB4 is the receptor for EphrinB2 on osteoblasts

Bidirectional signal: when they bind, osteoclast switched off and osteoblast swtich on; also inhibits osteoclast precursor differentation

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16
Q

Which cell is EphrinB2 found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

A

Which cell is EphrinB2 found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

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17
Q

Which cell is ephB4 receptor found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

A

Which cell is ephB4 receptor found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

18
Q

Which hormone increases ephrinB2 expression? [1]

A

PTH also increases ephrinB2 expression: When this ligand and receptor interact, there is prevention of the osteoclasts from activating but also stimulation of the osteoblasts

19
Q

Which drug can be used to determine how mineralised bone is? [1]

A

Tetracycline can be used to see how mineralised bone is. Tetracycline gets taken up on the calcium ions, and becomes deposited here and auto-fluoresces

20
Q

The vitamin D receptor is found on which cell?

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

A

The vitamin D receptor is found on which cell?

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

21
Q

Osteoblasts produce RANKL & OPG. State what their roles are in bone signalling [2]

A

RANKL:
* binds to RANK and stimulates osteoclastic bone resorption

osteoprotegerin (OPG)
* inhibits osteoclast differentiation, fusion, and activation
* protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK.

22
Q

State 3 molecules that inhibit bone resorption

A

transforming growth factor beta (TGF beta) (via increase in OPG)
interleukin 10 (IL-10)
osteoprotegerin (OPG)
calcitonin
* interacts directly with the osteoclast via cell-surface receptors

estrogen (via decrease in RANKL)
* stimulates bone production (anabolic) and prevents resorption
* inhibits activation of adenylyl cyclase

23
Q

Label A-E

A

A: calcified cartilage
B: chondrocytes
C: tide line
D: hyaline cartilage
E: articular surface

Hyaline cartilage: non-calcified
Deeper layers of cartilage are calcified: darker
Seperated via a tide mark

24
Q

Articular cartilage

Label A-E

A

A: tangenitial layer
B: transitional layer
C: radial layer
D: calcified cartilage
E: bone

25
Q

Describe the MoA for the release of AN the role of proinflammatory cytokines in the pathophysiology of OA [3]

A

Once the chondrocytes become damaged, they release pro-inflammatory cytokines which causes inflammatory response in the rest of the joint:

  • increase the production of matrix metalloproteinases and ADAMT-4
  • reduce aggrecan production and type 2 collagen production
  • overall cartilage degradation
  • Local inflammation: IL-1, IL-6, TNF
26
Q
A
27
Q

Describe steps of OA to synovitis [3]

A

Bone and cartilage damaged
Inflammation
Synovitis (secondary to established bone and cartilage pathology); major cause of pain and loss of function)
-

28
Q

Describe key changes in pathology of OA

A
  • Repetitive excess mechanical loading is what leads to stress-induced signals in the articular cartilage
  • Chondrocyte cloning and hypertrophy
  • tidemark duplication, followed by osteophyte formation, bone microfractures, angiogenesis
29
Q

Name a gene that is known to contribute to OA pathogensis [1]

What is the effect of losing this gene [3]

A

HMGB2: high mobility group protein 2 (chromatin protein)

Loss of HMGB2, leads to superficial zone cell death, loss of progenitor cells, and reduced synthesis of ECM components

30
Q

Macroscopically articular cartilage goes through 3 phases of degeneration. What are they? [3]

A

Fibrillation: rougher with frilly edges, compared to the usual nice and smooth appearance
Erosion and cracking: these cracks bigger and bigger due to the hydronic action in the joint
Eburnation:
* Complete loss of cartilage
* Completely exposed bone becomes polished

31
Q

Microscopically what happens in pathogenesis of OA? [3]

A

Chondrocyte necrosis - more in superficial layers. Dead cells not removed: ECM contamination

Focal clumps or clones of chondrocytes
* Increased local proliferation
* Large Isogenic clusters
* (The middle zone normally contains evenly spread out layers of chondrocytes, yet in osteoarthritis there are isogenic clusters/focal clumps of chondrocytes due to increased local proliferation where they group together in areas)

Change from type II to type I cartilage
* Reduces thickness of articular cartilage & Duplicated tidemark

32
Q

What is happening in this slide of OA? [1]

A

Conversion of type II to type I collagen

33
Q

What happens biochemically in pathogenesis in osteoarthritis [4]

A
  • In early stages of OA articular cartilage thickens and swells - increased water
  • But loss of proteoglycans make it less compressible
  • Water moves in and out faster
  • Focal erosion of cartilage develops and chondrocytes die.
  • Disordered repair of adjacent cartilage occurs and an overall failure of synthesis of ECM occurs
  • Creates fibrillated cartilage
  • Bone underneath the cartilage is exposed: subchondral sclerosis and cysts occur
  • Overgrowth of bone at joint margins causes osteophytes
34
Q

Which area of articular cartilage does OA initiate in?

A: tangenitial layer
B: transitional layer
C: radial layer
D: calcified cartilage
E: bone

A

Which area of articular cartilage does OA initiate in?

A: tangenitial layer / superifical layer
B: transitional layer
C: radial layer
D: calcified cartilage
E: bone

35
Q

Which layer do chondrocytes die in?

A: tangenitial layer
B: transitional layer
C: radial layer
D: calcified cartilage
E: bone

A

Which layer do chondrocytes die in?

A: tangenitial layer
B: transitional layer
C: radial layer
D: calcified cartilage

Leave an empty hole, releasing their extracellular contents into the matrix which triggers calcification. Calcified cartilage is eventually digested by osteoclasts and replaced with bone

36
Q

Early OA is characterised by: [2]

Late OA is characterised by: [2]

A

Early OA:
* loss of superficial zone and changes to the ECM of articular cartilage
* cell clusters emerge

Late OA
* continued loss of ECM
* chondrocyte hypertrophy

37
Q

Describe final stage; of OA impacting the subchondral bone

A

As articular cartilage is eroded, the underlying bone is exposed:
* There is microfractures of the trabeculae,
* increased osteoblastic activity and new bone formation
* resulting in subchondral sclerosis
* The surface also undergoes focal pressure necrosis, which leads to subarticular cysts forming.
* There is vascular engorgement, which slows blood flow, and there is bone marrow oedema.

38
Q

OA

What change has undertaken at A [1]?

A

Eburnation of cartilage: complete loss of cartilage, exposing bone

39
Q

OA

What change has undergone at the A? [1]

A

Eburnation of cartilage: complete loss of cartilage, exposing bone

40
Q

OA

Name the change that the arrow is pointing to [1]

A

Fibrillation: saw tooth surface irregularity of cartilage

41
Q

OA

Name the change that the arrow is pointing to [1]

A

A-Fibrillation of the articular cartilage (arrow)

42
Q

OA

Name the change that the arrow is pointing to [1]

A

Eburnation of articular cartilage