Lecture 27 - Healthy Bone

Question 1

Cortical bone is the ___ layer

Answer 1

outer

Question 2

Cancellous (trabecular) bone provides structural integrity __ the bone

Answer 2

inside

Question 3

Collagen is___ of adult bone mass

Answer 3

10%

Question 4

_________ is the major mineral in bone

Answer 4

Hydroxyapatite - insoluble salt of Ca and phosphorus = 65% of adult bone mass

Question 5

Water accounts for __% of bone mass

Answer 5

25%

Question 6

about ___% of our bone is replaced each year

Answer 6

5-10% - bONE REMODELLING

Question 7

Bone remodelling is initialted ________ throughout the skeleton

Answer 7

asynchronously

Question 8

bone provides __ of the bodys calcium

Answer 8

99% of Ca and 85% of phopshorus

Question 9

Bone is resorbed to release _____ into blood when required

Answer 9

calcium

Question 10

what else does bone remodelling allow?

Answer 10

adaptation of shape in resposne to biomechanical movement

repair of microdamage

Question 11

osteoclasts resorb bone leaving ____ _____

Osteoblasts then fill in that space, making _____

Answer 11

osteoclasts resorb bone leaving resoption cavities

Osteoblasts then fill in that space, making Osteoid (un-mineralised bone) - they eventually get mineralised

Question 12

Osteoctyes are embedde in the ___ ____

Answer 12

bone matrix- critical for controlling bone remodelling

Question 13

Trobecular can become thinnerover time, causing…

Answer 13

osteophorosis - bone is more likely to fracture

Question 14

Net bone gain can be called..

Answer 14

Osteopetrosis

Osteosclerosis

High bone mass

Question 15

osteoclasts are Large _____ cells, enriched with ____

Answer 15

osteoclasts are Large multinucleated cells, enriched with mitochrondria (to use energy to resorb bone)

Question 16

set through how osteoclasts resorb bone:

Answer 16

1) Forming a ‘sealing zone’ by intergin-mediated attachment to bone
2) acidification of resorptive lacunae to dissolve the mineral component
3) Release of callagenases and other enzymes to degrade the organic component
4) Bone degradation products are taken up by the osteoclasts and released

Question 17

The process of bone resorbtion takes about

Answer 17

3 weeks

Question 18

osteoblasts stem from a ______ skeletal stem cell

Answer 18

osteoblasts stem from a mesenchymal skeletal stem cell

also differentiate to muscle cells

Question 19

Following cessation of osteoprogenitor proliferation, osteoblasts:

secrete _____proteins (osteoid) including ____, bone ______, _______

express ______phophatase

renders the osteoid competent for ______ _______

Answer 19

secrete ECM proteins (osteoid) including collagen, bone sialoprotein, ostecalcin

express alkaline phophatase

renders the osteoid competent for mineral deposition

Question 20

How long is the bone forming process?

Answer 20

3-4 month long

Question 21

osteoclast are from a _______stem cell precursor

Answer 21

osteoclaast are from a haemopoetic stem cell precursor

common with macrophages

Question 22

RANKL (provided by osteoblasts) will bind to ___ (on osteoclast precursors) and promote bone-resorbing

Answer 22

RANKL will bind to RANK (on osteoclast precursors) and promote bone-resorbing

Question 23

Osteoblasts can also provide an inhibtor to RANKL called

Answer 23

OPG - decoy receptor

Question 24

If you take RANKL away, the osteoclasts will..

Answer 24

die

Question 25

Mice with RANK-/- develop severe

Answer 25

osteophorosis

Question 26

The negative inhibitor for RANKL is

Answer 26

OPG - Osteoprotegerin

Question 27

True or False

OPG is structurally distinct from RANKL

Answer 27

true

Question 28

_____ is the essential cytokine required for osteoclast differentiation, survival and fucntion

Answer 28

RANKL

Question 29

__ligands promote osteoblast differentiation and function

Answer 29

Wnt

Question 30

Wnt signals through Beta-catenin - to act on gene transcription to help..

Answer 30

Osteoblasts bone formation

Question 31

Wnt ligands are soluble factors that act by binding the co-receptors ____and _____ or _____

Answer 31

Wnt ligands are soluble factors that act by binding the co-receptors Frizzled and LRP5 or LRP6

This results in stabilisation of the signalling intermediate beta-catenin within the cytoplasm

Question 32

B-catenin participates in gene transcription causing…

Answer 32

osteoblast differentiation

can aso inhibit osteoclast differentiation

Question 33

What are the inhibitors of the Wnt signal pathway?

Answer 33

sFRP-1
DKK-1
Sclerostin

Question 34

which out of

sFRP-1
DKK-1
Sclerostin

interact with Wnt ligands and which affect the co-receptor complex?

Answer 34

DKK-1
Sclerostin
- prevent Wnt signalling by bindLRP5 or LRP6 preventing these coreceptors from interacting with Frizzled

sFRP-1 inhibits by binding to Wnt ligands themselves

Question 35

The most abundant bone cells are the

Answer 35

Osteocytes 20-25 yrs

Question 36

osteocytes sit within the bone matrix in ____

Answer 36

lacunae

Question 37

osteoctyes express both ____and___ as a means to regulate bone formation

Answer 37

osteoctyes express both sclerostin and DKK-1 as a means to regulate bone formation

Question 38

Bisphophoantes inhibit

Answer 38

osteoclast activity

Question 39

Anti-RANKL antibody inhibits

Answer 39

osteoclast differentiation and survival

Question 40

___ 1-34 acts to increase the maturation of osteoprogenitor stem cells as well as sclerostin and DKK1

Answer 40

rpPTH 1-34 acts to increase the maturation of osteoprogenitor stem cells as well as sclerostin and DKK1