Bone Turnover Flashcards

1
Q

Inflammatory mediators

A

Cytokines

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2
Q

Cytokines

A

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

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3
Q

Redundancy of cytokines system

A

Most functions of cytokines can be performed by many different cytokines

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4
Q

Pleiotropism of cytokine system

A

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

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5
Q

Hormone mediators of osteoclast differentiation and activity

A

1,25 dihydroxyvitamin D
Parathyroid hormone
Oestrogen
Leptin

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6
Q

Paracrine/autocrine mediators of osteoclast differentiation and activity

A

Prostaglandins
Interleukin-1
Interleukin-6
Tumour necrosis factor TNF

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7
Q

Osteoprotegerin OPG (or osteoclastogenesis inhibitory factor OCIF)

A

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

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8
Q

Derivation of osteoblasts

A

Mesenchymal stem cells

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9
Q

Effect of OPG

A

Inhibits osteoclast formation, function and syrvival

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10
Q

RANK ligand

A

Stimulates osteoclast formation, function and survival

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11
Q

What does RANK stand for

A

Receptor activator of nuclear factor K

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12
Q

How does osteoprotegerin work

A

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

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13
Q

Coupling

A

Bone formation occurs at sites of previous bone resorption

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14
Q

Balance - bone remodelling

A

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

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15
Q

Derivation of osteoclasts

A

Haematopoietic stem cells

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16
Q

Bone resorption

A

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

17
Q

Bone modelling

A

Gross shape is altered, bone added or taken away

18
Q

When does bone modelling occur

A

During growth
Sculpt adult shape

19
Q

Bone remodelling

A

All of bone is altered, new bone replaces old bone

20
Q

Function of bone remodelling

A

Remove and replace old bone
Mobilise minerals for homeostasis

21
Q

When does bone remodelling occur

A

In adult

22
Q

Bone remodelling process

A

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

23
Q

Primary osteons

A

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

24
Q

Secondary osteons

A

Cut through layers of lamellae and drive remodelling

25
Q

What are osteoclasts driven by

A

RANK-ligand/OPG balance

26
Q

What are osteoblasts driven by

A

Cytokines
Growth factors

27
Q

Wnt pathway

A

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

28
Q

LRP5 mutation

A

Stimulates osteoblasts to make more hine

29
Q

Sclerostin

A

Secreted glycoprotein
Down regulates Wnt signalling

30
Q

Wnt pathway function

A

Bone formation and decreased bone resorption

31
Q

Function of RANK-ligand

A

Induces osteoclast activity

32
Q

Stages of bone formation and remodelling

A

Activation
Resorption
Reversal
Formation
Quiescence

33
Q

Activation

A

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

34
Q

Resorption

A

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

35
Q

Reversal

A

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

36
Q

Formation

A

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

37
Q

Quiescence

A

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