Bone Turnover

Question 1

Inflammatory mediators

Answer 1

Cytokines

Question 2

Cytokines

Answer 2

A group of proteins and peptides that are used to allow one cell to communicate with anither

Question 3

Redundancy of cytokines system

Answer 3

Most functions of cytokines can be performed by many different cytokines

Question 4

Pleiotropism of cytokine system

Answer 4

A single cytokine has many different functional effects on many different cell types or even on the same cell

Question 5

Hormone mediators of osteoclast differentiation and activity

Answer 5

1,25 dihydroxyvitamin D
Parathyroid hormone
Oestrogen
Leptin

Question 6

Paracrine/autocrine mediators of osteoclast differentiation and activity

Answer 6

Prostaglandins
Interleukin-1
Interleukin-6
Tumour necrosis factor TNF

Question 7

Osteoprotegerin OPG (or osteoclastogenesis inhibitory factor OCIF)

Answer 7

Member of the tumour necrosis factor receptor superfamily
Inhibits the differentiation of myeloid precursors into osteoclasts
Decreases resorption by osteoclasts in vitro and in vivo

Question 8

Derivation of osteoblasts

Answer 8

Mesenchymal stem cells

Question 9

Effect of OPG

Answer 9

Inhibits osteoclast formation, function and syrvival

Question 10

RANK ligand

Answer 10

Stimulates osteoclast formation, function and survival

Question 11

What does RANK stand for

Answer 11

Receptor activator of nuclear factor K

Question 12

How does osteoprotegerin work

Answer 12

Binding to RANK-ligand, thus blocking the RANK-RANK ligand interaction between osteoblasts/stromal cells and osteoclast precursor

Question 13

Coupling

Answer 13

Bone formation occurs at sites of previous bone resorption

Question 14

Balance - bone remodelling

Answer 14

Amount of bone removed by osteoclasts should be replaced by osteoblastic activity

Question 15

Derivation of osteoclasts

Answer 15

Haematopoietic stem cells

Question 16

Bone resorption

Answer 16

Osteoclasts break down bone
Calcium is taken from bone and placed into bloodstream
Lysosomes assist the process
Calcium and phosphate are released

Question 17

Bone modelling

Answer 17

Gross shape is altered, bone added or taken away

Question 18

When does bone modelling occur

Answer 18

During growth
Sculpt adult shape

Question 19

Bone remodelling

Answer 19

All of bone is altered, new bone replaces old bone

Question 20

Function of bone remodelling

Answer 20

Remove and replace old bone
Mobilise minerals for homeostasis

Question 21

When does bone remodelling occur

Answer 21

In adult

Question 22

Bone remodelling process

Answer 22

Cells lining the bone surface are activated to form/recruit osteoclasts in response to injury
Osteoclasts attach to surface and projections increase surface area and secrete acid- dissolving the bone mineral to form resorption cavities (pits)
Osteoblasts are recruited to the resorbed bone and secrete osteoid matrix (mainly collagen)
Over time osteoid matrix becomes mineralised to form bone

Question 23

Primary osteons

Answer 23

Fill in holes that are left during very rapid formation
Don’t cut through the lamellae

Question 24

Secondary osteons

Answer 24

Cut through layers of lamellae and drive remodelling

Question 25

What are osteoclasts driven by

Answer 25

RANK-ligand/OPG balance

Question 26

What are osteoblasts driven by

Answer 26

Cytokines Growth factors

Question 27

Wnt pathway

Answer 27

Activation leads to a series of events Number of genes play a role in regulating bone Eg naked, dkk1, drosophila-frizzled hair, LRP5

Question 28

LRP5 mutation

Answer 28

Stimulates osteoblasts to make more hine

Question 29

Sclerostin

Answer 29

Secreted glycoprotein Down regulates Wnt signalling

Question 30

Wnt pathway function

Answer 30

Bone formation and decreased bone resorption

Question 31

Function of RANK-ligand

Answer 31

Induces osteoclast activity

Question 32

Stages of bone formation and remodelling

Answer 32

Activation Resorption Reversal Formation Quiescence

Question 33

Activation

Answer 33

pre-osteoclasts are attracted to the bone remodelling sites, activated by RANK ligand produced by osteoblasts • Pre-osteoclasts fuse to form multinucleated osteoclasts

Question 34

Resorption

Answer 34

osteoclasts dig out a resorption pit in spongy bone or burrow a tunnel in compact bone by releasing acid and cathepsin K • Osteoclasts disappear

Question 35

Reversal

Answer 35

mesenchymal stem cells appear along the burrow or pit and proliferate and differentiate into pre-osteoclasts

Question 36

Formation

Answer 36

they mature into osteoblasts at the surface of the burrow or pit and release osteoid at the site, forming a new soft non-mineralised matrix • The new matrix is then mineralised with calcium and phosphate

Question 37

Quiescence

Answer 37

the site, with resting lining cells, remains dormant until the next cycle • Osteoprotegerin mops up any RANK ligaments to prevent unnecessary remodelling