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Musculoskeletal > Cellular structure of bone > Flashcards

Cellular structure of bone Flashcards

1
Q

What are the functions of bone?

A
  • Support and movement as it is the attachment site for muscles
  • Protection for internal organs
  • Provides home for bone marrow
  • Acts as a mineral reservoir
  • Endocrine: source of some “non-classical” hormones
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2
Q

How does the bone support movement?

A

System of joints and levers together with the muscle system

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3
Q

What does the bone marrow do?

A

Produces blood cells and other types of stem cells

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4
Q

What part of the bone acts as a mineral reservoir?

A

Serum calcium (extracellular calcium) that is tightly regulated as an important mineral source for calcium and phosphate

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5
Q

How does bone act as a endocrine organ?

A

It secretes signalling molecules and some of which reach the circulatory and act in the classical sense

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6
Q

Describe the two structures in bone

A
  • Cortical (compact) bone

- Trabecular (spongy, cancellous) bone

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7
Q

What is cortical bone?

A
  • Organised in a highly organised manner
  • Forms the outer surface of long bones and flat bones
  • Organised in repeating units called osteons around central canals called haversian canals
  • Minute network of canals called lacunae that permeate throughout the structure
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8
Q

What are osteons?

A

Osteons are circular sheets or lamellae of bone matrix/tissue around central canals called Haversian canals

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9
Q

What do Haversian canals contain?

A

They contain blood vessels, nerves etc

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10
Q

What is trabecular bone?

A
  • Located inside the bone - underneath the cortical bone
  • Located in the head of long bones
  • Like a meshwork of the bone matrix with spaces inbetween
  • Mostly has the same composition as cortical bone
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11
Q

What are the two typical types of bones?

A
  • Long bone

- Flat bone

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12
Q

What is the structure of long bones?

A

Composed of the head and the shaft

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13
Q

What is in the middle of the long bone?

A

Bone marrow filled cavity

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14
Q

Describe the normal composition of bone

A
  • Protein: organic osteoid matrix (25%)
  • Mineral (75%) - mixed with the osteoid matrix and is mainly calcium and phosphate
  • Cells
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15
Q

What is the composition of the organic protein matrix?

A

Mainly type 1 collagen

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16
Q

What is the purpose of the organic protein matrix (osteoid)?

A
  • For flexibility and tensile strength

- the strength of the bone resides here

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17
Q

What is tensile strength of bone?

A

The ability of bone to bend slightly to resistance the perpendicular forces (right angles).

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18
Q

What is the major component of bone mineral?

A

Hydroxyapatite

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19
Q

What are the other components of bone mineral?

A

Calcium and phosphate

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20
Q

What is the function of bone mineral?

A

Rigid, brittle and gives high compressive strength (longitudinally) which is important for the ability of the bone to bear load

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21
Q

What are the major bone cells?

A

Osteoblasts
Osteoclasts
Osteocytes

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22
Q

What do the mesenchymal (stromal) stem cells differentiate into?

A

They give rise to osteoblasts

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23
Q

What is the function of osteoblasts?

A

Responsible for forming the organic matrix of bone and promoting the mineralisation

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24
Q

How are osteocytes formed?

A

The osteoblasts terminally differentiate and become osteocytes found within the bone matrix.

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25
Q

What do osteoblasts secrete?

A

The bone matrix and intune themselves encased inside the bone matrix

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26
Q

What do cells of the haematopoietic stem cell lineage become?

A

Red blood cells (erythrocytes) and white blood cells

Osteoclasts

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27
Q

Where are osteoclasts found?

A

Found lining the inside of the cortical bone on the marrow cavity, large multi-nucleated cells and derive from the blood cell lineage

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28
Q

Summarise function of osteoblasts

A
  • Bone forming cells
  • Derived from mesenchymal stem cells
  • Secrete osteoid, collagen matrix of bone
  • Promote mineralisation of osteoid
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29
Q

What do the osteoclasts do?

A

Bone reabsorbing cells

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30
Q

What do bone reabsorbing cells do?

A

Essential digesting of the bone organic matrix and combined with release of the mineral content - hydroxyapatite - releasing calcium and phosphate.

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31
Q

What is unique about osteoclasts?

A

Large, multinucleate and in the final differentiation, they involve fusion of several precursor cells

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32
Q

How do osteoclasts work?

A
  • Attach to the surface of bone, either inside the Haversian canals or along the struts in trabecula bone or the inner surface of bone facing bone marrow forming a tight seal.
  • Secrete acid to dissolve bone mineral and enzymes to digest organic matrix and secrete proteolytic enzymes.
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33
Q

What is the most important proteolytic enzymes released by osteoclasts?

A

Cathepsin K that has a high affinity for type 1 collagen to dissolve bone and cartilage.

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34
Q

What controls the life cycle of osteoclasts?

A

Apoptosis

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35
Q

What are osteocytes?

A

Terminally differentiated osteoblasts

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36
Q

What is osteocytes encased in?

A

In bone mineral matrix (lacunae)

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37
Q

What do the dendrites on the osteocytes do?

A

They extend multiple dendrites via minute canals in bone matrix (canaliculi) connecting one lacuni to the other and lacunae to the surface. This forms the lacunocanalicular system.

38
Q

What is the lacunocanalicular system?

A

It maintains communication with bone surface and blood vessels.

39
Q

What do the osteocytes coordinate?

A

They coordinate osteoblast (cells forming new bone) and osteoclast (cells that reabsorb old bone) activity

40
Q

Define bone remodelling

A

The opposing processes of bone formation and bone reabsorption

41
Q

What is the remodelling unit?

A

It is on the surface or within the Haversian canal of cortical bone. It involves osteoclasts dissolving and reabsorbing old bone and osteoblasts replacing with new bone.

42
Q

What do the osteoblasts secrete and do?

A

They secrete osteoid which will mineralise and form new bone. This is bone recycling.

43
Q

Why is bone recycling important?

A

It is essential for normal skeletal health

44
Q

Is bone inert dead tissue?

A

Not

45
Q

Why is the bone remodelling process important?

A

It is critical to the differentiation and life cycle of bone.

46
Q

When do osteoclasts differentiate?

A

They differentiate in response to appropriate signals and then undergo apoptosis within a certain timeframe.

47
Q

When do osteoblasts differentiate and what happens to them?

A

Osteoblasts will terminally differentiate into osteocytes and remain embedded in the matrix or remain inert along the bone surface

48
Q

What are the four stages of bone remodelling?

A
  1. Activation
  2. Reabsorption
  3. Reversal
  4. Formation
49
Q

What is the activation step in bone remodelling?

A

Involves stimulation of osteoclast differentiation

50
Q

What is the reabsorption step in bone remodelling?

A

Phase governed by the lifecycle of the osteoclast - it’s duration of action.

51
Q

What is the reversal step in bone remodelling?

A

Involves the signals of termination of the osteoclast activity and promote further osteoblast differentiation and the apoptosis of osteoclast.

52
Q

What is the formation step in bone remodelling?

A

The formation of new bone

53
Q

What do the bone cells form?

A

They form the basic multicellular unit that moves along the surface of the bone recycling (reabsorbing old bone and laying down new bone).

54
Q

What controls remodelling?

A
  • Load-bearing exercise
  • Cytokines and other local signals
  • Endocrine signals
55
Q

How does load-bearing exercise affect bone remodelling?

A

There is bone loss, as seen in bedbound pts, as it is thought that by doing load-bearing exercise such as walking, this leads to micro-stress fractures, detected by osteocytes, that then coordinate remodelling itself. However, bedbound patients, there is noticeable loss of the density of the skeleton.

56
Q

How do cytokines and other local signals affect the bone remodelling process?

A

At the cellular level, the control is via a network of signalling molecules promoting differentiation or apoptosis of osteoclasts and osteoblasts.

57
Q

How does the endocrine system affect the bone remodelling process?

A

Oestrogen inhibits osteocyte apoptosis and promtes osteoclast apoptosis. It favours formation rather than reabsorption - promoting bone health - essential in both sexes. It is produced by aromatase and is essential for bone health.

58
Q

What induces osteoclast differentiation?

A

RANK ligand?

59
Q

What does RANK stand for?

A

Receptor activator of nuclear factor kappa-B

60
Q

What is RANK?

A

A transcription factor that when activated will promote osteoclast differentiation.

61
Q

Where is RANK located?

A

It is surface receptor on pre-osteoclasts that stimulates differentiation.

62
Q

How is the RANK receptor activated?

A

It is activated by RANK-ligand that is expressed by pre-osteoblasts, osteoblasts and osteocytes. It binds to the RANK receptor and stimulates osteoclast differentiation. This stimulates the activation stage in the remodelling process.

63
Q

What do the osteocytes secrete?

A

They secrete OPG (osteoprotogerin)

64
Q

What is OPG?

A

It is a decoy receptor released by the osteocytes and competes with RANK-ligand for the RANK receptor, preventing activation of RANK(-L).

65
Q

What is demunosab?

A

It is one of the more recent drugs used for the treatment of osteoporosis.

66
Q

What is osteoporosis?

A

Common disease with the loss of bone mineral density

67
Q

What is demunosab?

A

It is a human monoclonal antibody against RANK-L.

68
Q

What is the Wnt signalling pathway?

A

It is a complex signal pathway that is highly conserved in the animal kingdom involved in animal development.

69
Q

What is the Wnt signalling pathway needed for?

A

It is required for osteoblast differentiation.

70
Q

What is the Wnt pathway negatively regulated by?

A

It is negatively regulated by various factors including DKK (dickkopf) and sclerostin (SOST).

71
Q

What is WNT?

A

It is a signal protein that activates the WNT receptor, Frizzled.

72
Q

What is the WNT receptor and what is needed for it to work?

A

The WNT receptor is Frizzled and it needs the co-receptor, LRP5 to work.

73
Q

What happens when the WNT receptor is activated?

A

The receptor is activated and beta-catenin is released and acts as a transcription factor and promotes other particular differentiation pathways.

74
Q

What prevents full activation of WNT?

A

When DKK and SOST bind to the co-factor, LRP5. This will no longer activate the intracellular cascade. It acts as a brake - negative regulation.

75
Q

Why is OPG released by osteocytes?

A

It acts to inhibit osteoclast differentiation whereas RANK-L acts to enhance it.

76
Q

What do sclerostin and DDK do?

A

They are produced by osteocytes and act as a brake on osteoblast differentiation.

77
Q

What happens if sclerostin is decreased?

A

It results in an increase in osteoblast differentiation.

78
Q

What can sclerostin and RANK- L be used in?

A

Be used in drugs and developed in new drugs

79
Q

What are some very rare diseases of the bone?

A

Mutations affecting key signals - important and serious disease

80
Q

What is the less rare disease of the bone?

A

Osteomalacia

81
Q

What is osteomalacia?

A

The failure of bone mineralisation.

82
Q

What is ricketts?

A

Soft bones like cartilage in children, due to vitamin D deficiency. It can occur in the elderly.

83
Q

What is vitamin D required for?

A

It is an endocrine factor required for bone mineralisation.

84
Q

What is a common bone disease?

A

Osteoporosis

85
Q

What is osteoporosis?

A

Accelerated loss of bone mineral density/organic component by two standard deviations or more below the average peak of bone density of sex and ethnic group

86
Q

What is the downfall of osteoporosis?

A

More prone to fractures, suffered by the elderly, can be attributed to the weakening of the bone.

87
Q

What are some bone diseases caused by mutations?

A
  • Osteoporosis pseudoglioma
  • Sclerosteosis
  • van Buchem disease
  • Osteopetrosis
88
Q

What causes osteoporosis pseudoglioma?

A

Inactivation of LRP-5, WNT Co-receptor

89
Q

What causes sclerosteosis and van Buchem disease?

A

Mutation of SOST gene, inactivating sclerostin protein so there is excess bone mass.

90
Q

What causes osteopetrosis?

A

Mutation inactivates RANK-L protein. This prevents the reabsorption of bone.

91
Q

Describe the loss of bone density correlation with ageing

A

There is an overview of bone density loss with ageing through different ages and sexes. Peak bone density is 25-30 and there after it is a slow downhill process with somewhat accelerated in women due to reduced oestrogen levels in menopause

Musculoskeletal (4 decks)

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