The Physiology Of Bone

Front 1

What are the functions of bones?

Back 1

1. Rigidity and shape

2. Protection and support

3. Locomotion

4. Ion Storage

5. Haemopoesis

6. Regulation of energy metabolism

Front 2

What are the two basic types of bone? (based on ECM type)

Back 2

1. Lamellar

2. Woven

Front 3

What are the physiological and functional properties of lammelar bone?

Back 3

1. Mature bone

2. Collagen arranged in lammellae (sheets)

3. Mechanically strong

Front 4

What are the physiological and functional properties of woven bone?

Back 4

1. Immature / healing - pathological bone

2. Haphazard meshwork of collagen

3. Replaced by lamellar bone.

Front 5

What are the types of lamellar bone?

What bones fall under each type?

Back 5

1. Cortical - long bones

2. Trabecular - vertebrae

Front 6

How is trabecular bone distinct from cortical bone?

Back 6

1. Thin cortical shell

2. 'Trabeculae' with connectivity increase compressive stress resitance

Commonly known as 'Spongy Bone'

Front 7

What is the majority of the mass of the bone due to?

Back 7

Cortical bone - makes up the outer layer of the bone.

Front 8

What are the hallmark features of the periosteum?

Back 8

Fibrous membrane which is rich with nutrient capillaries.

Front 9

What are the hallmark features of trabecular bone?

Back 9

The internal region of the bone, made up of a honeycomb structure which resists compression.

Front 10

What are the hallmark features of the medullary cavity?

Back 10

1. Contains bone marrow

2. Rich in blood vessels

3. Site of blood cell formation (haematopoietic stem cells)

Front 11

Label:

Back 11

1. Spongy bone

2. Compact bone

3. Bone marrow

4. Nutrient vessel

5. Edosteum

6. Periosteum

7. Medullary cavity

8. Epiphyseal line

9. Cartilage

Front 12

What is an osteon / haversian system?

Back 12

These are the functional units of cortical bones.

Front 13

Describe, in words, an osteon.

Back 13

All blood vessels, lymphatic nerves, connective tissues are arranged in concentric rings (lamellae) surround a haversian canal.

Front 14

What are the mechanical properties of bone ultimately determined by?

Back 14

1. Rate of turnover

2. Collagen matrix

3. Size

4. Structure

5. Mineral density

Front 15

If you were to analyse the composition of a bone sourced from someone with osteoporosis what would be evident?

Back 15

Higher proportion of woven bone to cortical bone. 1:3 rather than 1:8 (50% increase)

Front 16

What are the process which are targeted when treating osteoporosis?

Back 16

1. Aimed at increasing bone formation

2. Decreasing bone loss

Front 17

What diseases could provide novel approaches to osteoporosis therapy?

Back 17

Excess bone diseases

i) Scelerosteosis

ii) Van Buchnen disease

Front 18

How often is the entire bone system remodelled?

Back 18

once every 7 years (a continuous process)

Front 19

What triggers increased bone remodelling?

Back 19

1. Mechanical forces

2. Dietary calcium

3. Vitamin D

4. Hormones

5. Signalling molecules - wnt signalling pathway is essential

Front 20

What hormones trigger increased bone remodelling?

Back 20

i) Parathyroid hormone (PTH)

ii) Growth hormone

iii) Oestrogen

Front 21

What hormones are intimately involved in calcium homeostasis?

Back 21

1. Parathyroid hormone (PTH)

2. Vitamin D

3. Calcitonin

Front 22

What is the role of calcitonin?

Back 22

Stimulates bone mineralisation.

Front 23

What is the progression of calcitonin's effects?

Back 23

1. Increase in blood calcium

2. Calcitonin release

3. Stimulates Ca2+ deposition in bones

4. Decreases calcium reuptake in the kidneys

Front 24

What are the effects of Vitamin D and PTH?

Back 24

Stimulate bone turnover (Calcium release)

Front 25

What is the progression of PTH and Vitamin D's effects?

Back 25

1. Decrease in blood calcium

2. Stimulation of Vitamin D and PTH release

3. Promotes Calcium uptake

4. Stimulates bone turnover - = calcium release

Front 26

What is the biochemical life cycle of vitamin D in the body?

Back 26

Begins life in an inactive form and becomes activated via hydroxylation in the liver and kidney

Front 27

What is the active form of Vitamin D called?

Back 27

Main active form is 1,25 hydroxy vitamin D (1,25(OH)2D) or Calcitriol

Front 28

What are the main three cell types involved in bone turnover?

Back 28

1. Osetocytes

2. Osteoclasts

3. Osteoblasts

Front 29

What are the overall stages of the bone remodelling cycle?

Back 29

1. Quiescence

2. Resorption

3. Reversal

4. Formation

5. Mineralisation

6. Quiescence

Front 30

What happens in the resorption phase of the remodelling cycle?

Back 30

Migration of mononuclear proosteoclasts to the bone surface where they form multinucleated osteoclasts.

Front 31

What happens in the reversal phase of the bone remodeling cycle?

Back 31

Mononuclear cells reappear on the bone surface following completion of resorption. These cells provide signals for osteoblast differentiation and migration.

Front 32

What happens in the formation phase of the bone remodeling cycle?

Back 32

Osteoblasts lay down new bone until the resorbed bone is completely replaced by the new bone.

The osteoblasts form a new osteoid.

Front 33

What happens in the mineralisation phase of the bone remodeling cycle?

Back 33

Osteoclast layer is subsequently calcified - which takes 3-4 months.

Front 34

What are osteoclasts?

Back 34

Osteoclasts are terminally differentiated cells which make up 90% of the total bone cells in an adult.

They are derived from osteoblasts.

Front 35

Where can osteoclasts be found?

What is their role?

Back 35

Osteoclasts can be found encased within the bond matrix. They are mechanosensory cells which are responsible for regulating bone structure and mass.

Front 36

What morphological properties of osteocytes allow them to fulfil their role?

Back 36

Osteocytes can communicate via dendritic processes which pass through cannaliculi

Front 37

What are osteoclasts?

Back 37

Osteoclasts are the bone resorbing cells of the bone.

Front 38

What are osteoclasts derived from?

Back 38

Derived from circulating monocytes / macrophages.

Front 39

How can an activted osteoclast be identified?

Back 39

Activated osteoclasts are multinucleated.

Front 40

What activation factors cause the activation of osteoclasts?

Back 40

1. RANK ligand ( Receptor activatior of nuclear factor KB Ligand)

2. M-CSF (monocyte - colony stimulation factor)

Front 41

What is the role of M-CSF in the bone remodeling cycle?

Back 41

Stimulates the proliferation of osteoclast progenitor cells.

Front 42

What is the role of RANK ligand in the bone remodeling cycle?

Back 42

RANK ligand controls differentiation by activating RANK

Front 43

Describe the process by which RANK ligand and M-CSF cause osteoclast mediated bone resorption.

Back 43

1. Monocytes recruited by action of M-CSF and RANK ligand

2. Monocytes adhere and differentiate into osteoclasts - Differentiation is activated by RANK ligand

3. Differentiated osteoclasts now being to divide

4. Osteoclast colony now begin to secrete H+ and lytic enzymes

Front 44

What are the lytic enzymes which cause the breakdown of bone?

What secretes them?

Back 44

1. Tartate resistant acid phosphatase (TRAP)

2. Cathepsin K (CATK)

Front 45

What are osteoblasts?

Back 45

Osteoblasts are bone forming cells which are derived from stem cells.

Front 46

What is the role of an osteoblast?

Back 46

Lays down matrix which later becomes mineralised. Division and differentiation stimulated by hormones / cytokines.

Front 47

What factors stimulate mesenchymal stem cell differentiation from stem cells?

Back 47

1. Epidermal GF

2. Insulin like GF

Front 48

What factors stimulate preosteoblast differentiation from mesenchymal stem cells?

Back 48

1. IGF1 (Insulin like growth factor)

2. FGF-2 (fibroblast growth factor)

3. TGF - Beta 1/2 (transforming growth factor)

4. Parathyroid hormone

5. Prostaglandins

6. Vitamin D3 (1,25(OH)2 D3)

Front 49

What factors stimulate osteoblast differentiation from preosteoblasts?

Back 49

Transcription factors:

1. Runx2

2. Beta catenin

3. Osterix

& same as before

1. IGF1 (Insulin like growth factor)

2. FGF-2 (fibroblast growth factor)

3. TGF - Beta 1/2 (transforming growth factor)

4. Parathyroid hormone

5. Prostaglandins

6. Vitamin D3 (1,25(OH)2 D3)

Front 50

What is the critical pathway involved in bone formation?

Back 50

wnt - Beta catenin signalling.

Front 51

What happens when the wnt signalling pathway is inactive?

Back 51

Beta catenin is phosphorylated by glycogen synthase kinase 3 (GSK-3)

Front 52

What is the effect of an inactive wnt - beta catenin signalling pathway?

Back 52

B catenin is targeted for degradation. Thus it does not enter the nucleus and therefore there is no target gene expression.

Front 53

What happens when wnt is present in the ECM?

Back 53

Wnt binds to the surface receptors - LRP/Frizzled complex. This causes B-Catenin to no longer be targeted for degradation as a key part of the inactivation complex - Axin becomes bound to LRP. Beta catenin subsequently enters the nucleus and activates target genes. (TCF)

Front 54

What is excessive bone growth termed as?

Back 54

Scelerosteosis.

Front 55

What type of genetic condition is sclerosteosis?

Back 55

An autosomal recessive condition.

Front 56

What causes sclerosteosis?

Back 56

A defect in the SOST gene results in decreased transcription and thus decreased translation of 'Sclerostin'.

Front 57

What is the role of sclerostin in the wnt signalling pathway?

Back 57

Sclerostin inhibits wnt signalling by acting as an LRP agonist.

Front 58

What is the molecular effect of decreased sclerostin expression?

Back 58

Reduced sclerostin expression = increased wnt signalling and thus increased bone formation via increases in osteoblast differentiation.