Bone Metabolism 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

Which molecule activates precursor osteoclast into activated osteoclast? [1]

A

RANKL

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3
Q

Which locations in bone tissue do you find osteoprogenitor cells? [2]

A
  • periosteum
  • endosteum
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4
Q

review bone histology

A
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5
Q

At birth, all bone marrow is [red / yellow]

As you age, bone marrow turns [red / yellow]

A

At birth, all bone marrow is red

As you age, bone marrow turns yellow

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6
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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7
Q

Which structure do osteocytes sense mechanical stress via? [1]

A

canaliculi: If the bone is very stressed and the canaliculi break, then the osteocytes cellular processes are damaged, which leads to osteocyte death and bone remodelling ensues

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8
Q

Asides from osteoblasts (which then can turn into osteoclasts), which cell type can osteoprogenitor cells differentiate into? [1]

A

Chondrocytes

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9
Q

Describe the composition of bone [3]

A

35-40% organic
* Type 1 collagen (90% tensile strength)
* Proteoglycans (compressive strength)
* Growth factors / cytokines / osteoid

60% inorganic
* 95% Calcium hydroxyapatite (Ca10(PO4)6(OH)2)
* Approximately 5% water

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10
Q

Describe the structure of collagen in bone [1]

Describe how calcium hydroxyapatite is structured on bone collagen [1]. Why is this significant [1]

A

Collagen in a triple helix

Calcium hydroxyapatite on intermittent blocks on collagen - so not too brittle

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11
Q

Osteoclasts are derived from which cell type? [1]

Where does this come from in the bone? [1]

A

Macrophage lineage - red bone marrow

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12
Q

What is the difference in structure between active and inactive osteoblasts? [2]

A

Cuboidal osteoblasts: active

Flattened osteoblasts: inactive

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13
Q

Which cell type is this?

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

A

Which cell type is this?

osteoclast

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14
Q

Which molecule signals healthy bone structure?

RANLK
OPG
Sclerostin
PTH

A

Sclerostin: high levels of sclerostin switches OFF osteoblasts

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15
Q

Describe the mechanism of osteocytes and the production of sclerostin when mechanical stress occurs [2]

A

Osteocytes sense mechanical stress of bone: death of osteocytes signals remodelling
* Healthy osteocytes produce sclerostin and switch OFF osteoblasts
* Damaged osteocytes: stops producing sclerostin and osteoblasts do not have inhibitory signal / become active

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16
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

17
Q

Which cell is EphrinB2 found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

A

Which cell is EphrinB2 found on

osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte

18
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

19
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

20
Q

Describe the mechanism that occurs for bone remodelling [4]

What is the trigger for bone remodelling to occur? [1]

A

Trigger: No sclerostin produced:

  1. osteoclast moves in and clamps over damaged bone
  2. Produce HCl & enzymes which dissolves the bone
  3. bones and proteins (Ca2+) cross osteoclast to exit into interstitial fluid
  4. osteoblasts move in and fill with osteoid (unmineralised bone)
  5. Osteoid is mineralised approximately 1 week after the initial osteoid is put down in the lacunae.
21
Q

Label A-E

A

A: osteoblast
B: osteoclast
C: osteoid
D: cement line
E: mineralized bone

22
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

23
Q

What level of total serum calcium should have in the body? [1]

What should be free ionised calcium levels? [1]

A

Serum calcium level 2.2 - 2.6mmol/L (8.5-10.5 mg/dL)

Free ionized calcium 1.0-1.25mmol/L (0.05% of total Ca2

24
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)
25
Q

Which receptor does FGF23 bind to? [1]

What is the effect of FGF23 activation? [2]

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

26
Q

Which of the following is the principal phosphaturic hormone

Sclerostin
FGF23
PTH
RANKL

A

Which of the following is the principal phosphaturic (excreted in urine) hormone

Sclerostin
FGF23
PTH
RANKL

27
Q

Name 5 RANKL inducers [3]

Name 1 RANKL inhibitor [1]

A

Inducers
TNF-a
IL-1
Prostaglandin E2

Inhibitors
Oestrogen

28
Q

FGF23 effect on PTH? [1]

A

Switches off PTH

29
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

30
Q

Describe the physiological effects of calcitonin [3]

A
  • inhibits osteoclast differentiation and activity
  • increases Ca2+ excretion from kidney
  • Inhibits Ca2+ absorption by intestines
31
Q

Describe effect of oestrogen at the:

Gut [1]
Bone [1]

A

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

32
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

33
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

34
Q

Ca2+ homeostasis

Describe effect of glucocorticoids at the:

Gut [1]
Bone [1]

A

Gut - decrease Ca2+ absorption

Bone - increased re-absorption/decreased formation

35
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

36
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

37
Q

Prolonged corticosteroid treatment leads to which disease? [1]

A

osteoporosis

38
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

39
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