3/6/17 Bone Resorption: Osteoclast Formatio and Regulation

Question 1

Phase turned on first in bone remodelling:

Answer 1

osteoclast resorption, reversal, osteoblast/ formation

Question 2

About how many factors are involved in bone remodelling?

Answer 2

100s

Question 3

Bifunctional role of Wnt-signalling pwy:

Answer 3

regulation of blast and last differentiation

Question 4

What diverts mesenchymal stem cell down the pwy of blast differentiation?

Answer 4

Wnt signalling

Question 5

This leads prevents blast proliferation and differentiation:

Answer 5

DKK-1 binding Wnt receptor complex on blast lineage cell surface

Question 6

How do precursors of the mature osteoblast enhance bone resorption?

Answer 6

by boosting RANKL induced osteoclastogenesis

Question 7

Blockade of DKK-1 leads to:

Answer 7

progression of blast differentitation

Question 8

Upregulation of OPG leads to:

Answer 8

blocking RANKL-induced osteoclastogenesis, inhibition of bone resorption

Question 9

What leads to upregulation of OPG?

Answer 9

Activation of Wnt signalling pwy

Question 10

Precursors to pre osteoclasts;

Answer 10

monos, macs

Question 11

How are multinucleated cells formed?

Answer 11

mononuclear cells fuse, make clasts

Question 12

Portion of clast that attached to bone to be resorbed:

Answer 12

ruffled border

Question 13

This factor downregulating WNT pwy, inhibiting differentiation of mesenchymal cells:

Answer 13

DKK-1

Question 14

What can induce DKK-1?

Answer 14

TNF-a

Question 15

What will form if mesenchymal stem cells go down the path of endochondral bone formation?

Answer 15

chondrocyte

Question 16

This is a coupling agent in bone forming/ absorbing:

Answer 16

RANKL

Question 17

OPG sf:

Answer 17

osteoprotegerin

Question 18

Ratio of these is important in formation of osteoclasts:

Answer 18

OPG and RANKL

Question 19

Factors that stimulate blast expression of RANK Ligand:

Answer 19

TNF-a, PTHrP, IL-1, 6, 11, Vit D, Glucocorticoids, PTH, PGE2, local factors: cytokine, inflammation

Question 20

PTHrP is involved in:

Answer 20

bone mineralization (PTH related protein)

Question 21

How does PTH influence blast activity:

Answer 21

receps on blasts for PTH

Question 22

Precursors for clasts:

Answer 22

CFU-macs

Question 23

TF? RANKL is made by clasts and influence blast activity.

Answer 23

F vice versa, act on prefusino clasts

Question 24

Decoy receptor that prevent RANKL-RANK binding:

Answer 24

OPG

Question 25

OPG inhibits:

Answer 25

calst formation, function, and survival

Question 26

3 general groups that induce blasts to release RANKL:

Answer 26

hormones, GF's, cytokines

Question 27

There is cross talk bw:

Answer 27

immune cells and bone cells

Question 28

immunoregulatory cytokines influence:

Answer 28

fate of bone cells, helps explain inflammatory rxn in RA, PDD and bone loss

Question 29

All cells of the mammalian immune system are derived from:

Answer 29

HSC (hemat..)

Question 30

Cell types that can produce RANKL:

Answer 30

T cells, gingival fibroblasts/PDL cells, blasts

Question 31

TF? The release of RANKL, wo OPG, will always lead to monocyte/ preosteoblasts.

Answer 31

T

Question 32

Cells that produce the most RANK in pdd, leading to bone resorption

Answer 32

T cells

Question 33

Cytokines and inflammatory mediators that can stimulate clast formation and bone resorption, all implicated in inflammation induced bone resorption:

Answer 33

IL-1, 6, 11, 17, TNFa, LIF, OSM, Bradykinin, Kallidin, Thrombin

Question 34

Cytokines and inflammatory mediators that can inhibit blastic cells

Answer 34

IL, 4, 10, 12, 13, 18, IFN-B, IFN-y

Question 35

IL-1, 6, 11, 17, TNFa, LIF, OSM, Bradykinin, Kallidin, Thrombin all act directly on these cells:

Answer 35

blasts, stromal cells

Question 36

High RANKL/ OPG ratio will lead to:

Answer 36

clast formation, bone resorption

Question 37

IL, 4, 10, 12, 13, 18, IFN-B, IFN-y directly inhibit these cells:

Answer 37

blasts, stromal cells, osteoclast progenitors

Question 38

Where in the cycle do chemokines exert their influence?

Answer 38

on clast progenitor cells, distal to RANKL/OPG

Question 39

Concentrations of these need to be evaluated to determine whether bone will be lost or not:

Answer 39

RANKL/ OPG

Question 40

Role of IL, 4, 10, 13, IFN-y:

Answer 40

inhibit RANKL and the cytokines that stimulate it

Question 41

Factors that stimulate RANKL:

Answer 41

IL 1, 6, 7, 11, 17, TNFa, LIF, OSM

Question 42

Effect of PGE2 on RANKL:

Answer 42

upregulates

Question 43

TF? TNF acts indirectly on RANKL production.

Answer 43

T

Question 44

These upregulate preosteoblasts:

Answer 44

CXCL 10, 12, 13, CCL5, PGE2, PGI2, PGF2a, GFs: FGF, PDGF, BMP2, TGFB, IGF

Question 45

This mediator of inflammation works on both the clastic and blastic side:

Answer 45

PGE2

Question 46

Upregulate clast precursors:

Answer 46

RANKL, TNF, M-CSF

Question 47

These indirectly stimulate osteoclastogenesis by effects on RANKL, M-CSF, or TNF-a:

Answer 47

cytokines or lipid based mediator such as prostaglandins or leukotrienes

Question 48

These stimulate recruitment of clast precursors or clast activity:

Answer 48

chemokines

Question 49

During inflammatory conditions, inc production of more cytokines w IL-1,6,7,11,17, TNF-a, LIF, OSM and RANK are primarily produced by:

Answer 49

leukocytes

Question 50

These are released from bone matrix or synthesized locally by various cell types after bone resorption and stimulate proliferation of blast precursor, osteoblast differentiation, or synthesi of bone matrix

Answer 50

GFs like FGF, PDGF, BMP-2, TGF-2, IGF

Question 51

These may affect bone formation by effects on blast precursors or blasts:

Answer 51

chemokines like CXCL10, 12, 13, CCL5

Question 52

stopped at slide 11

Answer 52

ok