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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

What does the bone marrow do?

A

Produces blood cells and other types of stem cells

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3
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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4
Q

Describe the two structures in bone

A
  • Cortical (compact) bone
  • Trabecular (spongy, cancellous) bone
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5
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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6
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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7
Q

What do Haversian canals contain?

A

They contain blood vessels, nerves etc

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8
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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9
Q

What are the two typical types of bones?

A
  • Long bone - Flat bone
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10
Q

What is the structure of long bones?

A

Composed of the head and the shaft

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11
Q

What is in the middle of the long bone?

A

Bone marrow filled cavity

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12
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 + HYDROXYAPATATITE
  • Cells
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13
Q

What is the composition of the organic protein matrix?

A

Mainly type 1 collagen

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14
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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15
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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16
Q

What is the major component of bone mineral?

A

Hydroxyapatite

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17
Q

What are the other components of bone mineral?

A

Calcium and phosphate

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18
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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19
Q

What are the major bone cells?

A
  • Osteoblasts
  • Osteoclasts
  • Osteocytes
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20
Q

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

A

They give rise to osteoblasts

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21
Q

What is the function of osteoblasts?

A

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

22
Q

How are osteocytes formed?

A

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

23
Q

What do osteoblasts secrete?

A

The bone matrix and intune themselves encased inside the bone matrix

24
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

25
Q

Summarise function of osteoblasts

A

FORM NEW BONE

  • Derived from mesenchymal stem cells
  • Secrete osteoid, collagen matrix of bone
  • Promote mineralisation of osteoid
26
Q

What do the osteoclasts do?

A

Bone reabsorbing cells

27
Q

What do bone reabsorbing cells do?

A
  • Secrete acid to dissolve bone mineral and enzymes to digest organic matrix
  • Enzyme is CATHEPSIN K (proteolytic enzyme, breaks down bone and cartilage, acid dissolves bone mineral content)
  • Life cycle of bone dissolving and reabsorbing cells is controlled by apoptosis

(hydroxyapatite is dissolved by the acid releasing calcium and phosphate)

28
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.

29
Q

What are osteocytes?

A

Terminally differentiated osteoblasts

  • Encased in bone mineral matrix (lacunae)
  • Extend multiple dendrites via minute canals in bone matrix (canaliculi)
  • Lacunocanalicular system maintains communication with bone surface and blood vessels
  • Master coordinator: Thought to coordinate osteoblast and osteoclast activity through lacunocanalicular system
30
Q

What do the osteocytes coordinate?

A

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

31
Q

Define bone remodelling

A

The opposing processes of bone formation and bone reabsorption

32
Q

What do the osteoblasts secrete and do?

A

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

33
Q

When do osteoclasts differentiate?

A

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

34
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

35
Q

What are the four stages of bone remodelling?

A
  1. ACTIVATION = stimulation of osteoclast differentiation
  2. REABSORPTION = Duration of action of osteoclast
  3. REVERSAL = signals terminate osteoclast acitivity and promote further osteoblast differentiation, apoptosis of osteoclast
  4. FORMATION = formation of new bone
36
Q

What controls remodelling?

A
  • Load-bearing exercise - Co-ordinates remodelling, bed bound patients - loss of density of skeleton
  • Cytokines and other local signals = promote differentiation of osteoclasts and blasts
  • Endocrine signals
37
Q

What hormone is involved in bone remodelling?

A

Oestrogen inhibits osteocyte apoptosis and promtes osteoclast apoptosis.

  • Promotes bone health
  • Produced by aromatase
38
Q

How is osteoclast differentiation induced by the rank ligand?

A

RANK ligands are produced by pre-osteoblasts, osteoblasts and osteocytes these bind to RANK and stimulate osteoclast differentiation

  • RANK (receptor activator of nuclear factor kappa-B): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation by binding to the RANK ligand
  • Binding of the RANK ligand to the RANK cell surface receptor will activate the transcription factor NF-kB promoting differentiation of pre-cursors into osteoclasts
39
Q

What does OPG do?

A
  • decoy receptor produced by osteocytes; binds to RANK, preventing activation by RANK-L
40
Q

What is the Wnt signalling pathway?

A
  • This pathway is required for osteoblast differentiation
  • Wnt is a signalling protein molecule which acts a receptor called frizzled
  • Frizzled requires a co-receptor LRP5
  • Following Wnt binding and frizzled activation beta catenin becomes released acting as a transcription factor and allows for osteoblast differentiation.
41
Q

What hormones will negatively regulate the Wnt pathway?

A

DKK (dickkopf) and sclerostin

42
Q

What is the less rare disease of the bone?

A

Osteomalacia = weakening and softening of the bone, more prone to fractures due to failure of mineralisation

43
Q

What is ricketts?

A

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

44
Q

What is vitamin D required for?

A

It is an endocrine factor required for bone mineralisation.

45
Q

What is a common bone disease?

A

Osteoporosis

46
Q

What is osteoporosis?

A

loss of bone density, Increase in bone resorption over formation, increased fracture risk

47
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.

48
Q

What are some bone diseases caused by mutations?

A
  • Osteoporosis pseudoglioma
    • Inactivation of LRP-5, wnt signalling co-receptor - unable to function properly
  • Sclerosteosis van Buchem disease
    • Mutation of SOST gene, inactivating sclerostin protein, excessive bone formation due to overactivation of Wnt signalling pathway
  • Osteopetrosis
    • Mutation inactivates RANKL protein
49
Q

What causes osteoporosis pseudoglioma?

A

Inactivation of LRP-5, WNT Co-receptor

50
Q

What causes sclerosteosis and van Buchem disease?

A

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

51
Q

What causes osteopetrosis?

A

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

52
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 (3 decks)

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