3/6/17 Bone Resorption: Osteoclast Formatio and Regulation Flashcards
Phase turned on first in bone remodelling:
osteoclast resorption, reversal, osteoblast/ formation
About how many factors are involved in bone remodelling?
100s
Bifunctional role of Wnt-signalling pwy:
regulation of blast and last differentiation
What diverts mesenchymal stem cell down the pwy of blast differentiation?
Wnt signalling
This leads prevents blast proliferation and differentiation:
DKK-1 binding Wnt receptor complex on blast lineage cell surface
How do precursors of the mature osteoblast enhance bone resorption?
by boosting RANKL induced osteoclastogenesis
Blockade of DKK-1 leads to:
progression of blast differentitation
Upregulation of OPG leads to:
blocking RANKL-induced osteoclastogenesis, inhibition of bone resorption
What leads to upregulation of OPG?
Activation of Wnt signalling pwy
Precursors to pre osteoclasts;
monos, macs
How are multinucleated cells formed?
mononuclear cells fuse, make clasts
Portion of clast that attached to bone to be resorbed:
ruffled border
This factor downregulating WNT pwy, inhibiting differentiation of mesenchymal cells:
DKK-1
What can induce DKK-1?
TNF-a
What will form if mesenchymal stem cells go down the path of endochondral bone formation?
chondrocyte
This is a coupling agent in bone forming/ absorbing:
RANKL
OPG sf:
osteoprotegerin
Ratio of these is important in formation of osteoclasts:
OPG and RANKL
Factors that stimulate blast expression of RANK Ligand:
TNF-a, PTHrP, IL-1, 6, 11, Vit D, Glucocorticoids, PTH, PGE2, local factors: cytokine, inflammation
PTHrP is involved in:
bone mineralization (PTH related protein)