Bone Metabolism Flashcards
Which cell makes type 1 collagen?
osteoclasts
osteoblasts
osteocyte
osteoprogenitor
Which cell makes type 1 collagen?
osteoclasts
osteoblasts
osteocyte
osteoprogenitor
Which molecule activates precursor osteoclast into activated osteoclast? [1]
RANKL
Which locations in bone tissue do you find osteoprogenitor cells? [2]
- periosteum
- endosteum
review bone histology
At birth, all bone marrow is [red / yellow]
As you age, bone marrow turns [red / yellow]
At birth, all bone marrow is red
As you age, bone marrow turns yellow
Name two places that may find red bone in an adult [2]
spongy / trabeculae bones of vertebrae, ribs, sternum, cranium and epiphyses of long bones
Which structure do osteocytes sense mechanical stress via? [1]
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
Asides from osteoblasts (which then can turn into osteoclasts), which cell type can osteoprogenitor cells differentiate into? [1]
Chondrocytes
Describe the composition of bone [3]
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
Describe the structure of collagen in bone [1]
Describe how calcium hydroxyapatite is structured on bone collagen [1]. Why is this significant [1]
Collagen in a triple helix
Calcium hydroxyapatite on intermittent blocks on collagen - so not too brittle
Osteoclasts are derived from which cell type? [1]
Where does this come from in the bone? [1]
Macrophage lineage - red bone marrow
What is the difference in structure between active and inactive osteoblasts? [2]
Cuboidal osteoblasts: active
Flattened osteoblasts: inactive
Which cell type is this?
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
Which cell type is this?
osteoclast
Which molecule signals healthy bone structure?
RANLK
OPG
Sclerostin
PTH
Sclerostin: high levels of sclerostin switches OFF osteoblasts
Describe the mechanism of osteocytes and the production of sclerostin when mechanical stress occurs [2]
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
Describe the role of EphrinB2 anad ephB4 [2]
On which cells are each located? [2]
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
Which cell is EphrinB2 found on
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
Which cell is EphrinB2 found on
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
Which cell is ephB4 receptor found on
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
Which cell is ephB4 receptor found on
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
Which hormone increases ephrinB2 expression? [1]
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
Describe the mechanism that occurs for bone remodelling [4]
What is the trigger for bone remodelling to occur? [1]
Trigger: No sclerostin produced:
- osteoclast moves in and clamps over damaged bone
- Produce HCl & enzymes which dissolves the bone
- bones and proteins (Ca2+) cross osteoclast to exit into interstitial fluid
- osteoblasts move in and fill with osteoid (unmineralised bone)
- Osteoid is mineralised approximately 1 week after the initial osteoid is put down in the lacunae.
Label A-E
A: osteoblast
B: osteoclast
C: osteoid
D: cement line
E: mineralized bone
Which drug can be used to determine how mineralised bone is? [1]
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
What level of total serum calcium should have in the body? [1]
What should be free ionised calcium levels? [1]
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
Describe action of increased PTH [3]
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)
Which receptor does FGF23 bind to? [1]
What is the effect of FGF23 activation? [2]
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
Which of the following is the principal phosphaturic hormone
Sclerostin
FGF23
PTH
RANKL
Which of the following is the principal phosphaturic (excreted in urine) hormone
Sclerostin
FGF23
PTH
RANKL
Name 5 RANKL inducers [3]
Name 1 RANKL inhibitor [1]
Inducers
TNF-a
IL-1
Prostaglandin E2
Inhibitors
Oestrogen
FGF23 effect on PTH? [1]
Switches off PTH
Where is calcitonin produced? [1]
What triggers calcitonin release? [1]
What is the effect of calcitonin? [1]
Calcitonin produced in thyroid gland
Produced when Ca2+ leves rise
Calcitonin reduces Ca2+ levels
Describe the physiological effects of calcitonin [3]
- inhibits osteoclast differentiation and activity
- increases Ca2+ excretion from kidney
- Inhibits Ca2+ absorption by intestines
Describe effect of oestrogen at the:
Gut [1]
Bone [1]
Gut - increased Ca2+ absorption
Bone - decreased re-absorption (inhibit osteoclasts)
Describe the effect of adding progesterone ceram to osteoporosis therapy [1]
increases bone density by around 10% in 1st 6 months to rate of 3-5% annually stabilises at levels of 35 year old
Describe the action of FSH on osteoclasts [1]
Describe the action of FSH on IL-1. TNF and IL6 [1]
Direct action on osteoclasts upregulates RANK
Indirect action on monocytes to secrete IL1, TNF and IL6
Ca2+ homeostasis
Describe effect of glucocorticoids at the:
Gut [1]
Bone [1]
Gut - decrease Ca2+ absorption
Bone - increased re-absorption/decreased formation
The vitamin D receptor is found on which cell?
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
The vitamin D receptor is found on which cell?
osteoblast
osteoprogrenitors
osteoclast
osteoid
osteocyte
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
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
Prolonged corticosteroid treatment leads to which disease? [1]
osteoporosis
Osteoblasts produce RANKL & OPG. State what their roles are in bone signalling [2]
RANKL:
* binds to RANK and stimulates osteoclastic bone resorption
osteoprotegerin (OPG)
* inhibits osteoclast differentiation, fusion, and activation
State 3 molecules that inhibit bone resorption
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
