B6.052 Prework 3: ARF Cycle, Bone Cell Interactions, Extrinsic and Intrinsic Influences

Question 1

ARF cycle

Answer 1

activation
resorption
reversal phase
formation
resting phase

Question 2

why are the actions of osteoblasts and osteoclasts interconnected?

Answer 2

there are NO receptors for PTH of vit D on osteoclasts
only calcitonin receptors
connection mediated by:
-RANK, RANK-L, osteoprotegerin
-TGFB

Question 3

function of calcitonin

Answer 3

weak antagonist of PTH
reduces serum Ca
decreases osteoclast activity

Question 4

discuss the dual effect of PTH on bone

Answer 4

PTH stimulates osteoblast proliferation via PTH1R on osteoblast
additionally, osteoblast will express RANKL to interact with RANK on osteoclasts
this induces osteoclast differentiation

Question 5

balanced vit D levels

Answer 5

calcium absorption meets metabolic demands

normal bone mineralization is maintained

Question 6

low levels of vit D

Answer 6

calcium reservoir of bone is depleted to correct for low calcium absorption in gut

Question 7

vitamin D receptors on osteoblasts

Answer 7

facilitate vit D induced proliferation, differentiation, and mineralization

Question 8

major mechanism of bisphosphonates

Answer 8

shifts balance to osteoblasts by inhibiting/killing osteoclasts
similar to effect of osteoprotegerin (OPG)

Question 9

function of osteoprotegerin in reference to RANK/RANKL

Answer 9

decoy receptor for RANKL

decreased osteoclastic activity

Question 10

what happens once osteoclasts start breaking down bones?

Answer 10

matrix bound growth factors become liberated > proliferation of osteoprogenitor cells > Wnt and BMP pathways stimulated > osteoblasts activated

Question 11

describe the Wnt pathways

Answer 11

Wnt released from osteoprogenitor cells
acts on LRP5/6 receptor on osteoblasts
stimulates B catenin pathway which drives osteoblastic activity
ALSO stimulates production of OPG which further tips balance toward osteoblasts

Question 12

where is sclerostin produced

Answer 12

osteocytes

inhibits osteoblasts