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MSS & Skin > MSS: Cellular Structure of Bone > Flashcards

MSS: Cellular Structure of Bone Flashcards

1
Q

Outline the functions of bone

A

Support and movement: attachment site for muscles
Protection for internal organs
Provides home for bone marrow
Acts as mineral reservoir
Endocrine: source of some ‘non-classical’ hormones

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2
Q

Describe the 2 types of bone structure

A

Cortical (compact) bone

Trabecular (spongy, cancellous) bone

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3
Q

What is the composition of bone?

A

Protein: organic osteoid matrix (25%)
Mineral (75%)
Cells

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4
Q

Describe the structure and function of the organic (osteoid) protein matrix

A

Mainly type 1 collagen
Gives both flexibility and tensile strength
Middle portion of bone

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5
Q

Name the common bone minerals

A

Hydroxyapatite
Calcium and phosphate (Ca10(PO4)6(OH)2)
found at Ends of bone

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6
Q

What is the purpose of bone minerals?

A

Rigid, brittle: gives high compressive strength

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7
Q

Name examples of bone cells

A

Osteoblasts
Osteoclasts
Osteocytes

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8
Q

What are the bone marrow cells?

A

Mesenchymal (stromal) stem cells

Haematopoietic stem cells

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9
Q

What are osteoblasts?

A

Bone forming cells derived from mesenchymal stem cells

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10
Q

What is the function of osteoblasts?

A

Secrete osteoid, collagen matrix of bone

Promote mineralization of osteoid

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11
Q

What are osteoclasts?

A

Large, multinucleate bone reabsorbing cells derived from haematopoietic stem cells

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12
Q

How is the osteoclast lifecycle mediated?

A

Life cycle controlled by apoptosis

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13
Q

What is the role of osteoclasts?

A

Secrete acid to dissolve bone mineral

Secrete enzymes to digest organic matrix

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14
Q

What are osteocytes?

A

Terminally differentiated osteoblasts

Mature quiescent osteoblasts on the bone surfaces are distinguished as bone lining cells

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15
Q

Describe the structure of osteocytes

A

Encased in bone mineral matrix (lacunae)

Extend multiple dendrites via minute canals in bone matrix (canaliculi)

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16
Q

Outline the function of osteocytes

A

Lacuno Canalicular system maintains communication with bone surface and blood vessels
Thought to coordinate osteoblast and osteoclast activity

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17
Q

Where does bone remodelling occur?

A

Occurs in all types of bones within the remodelling unit in trabecular bone or haversian units in cortical bone

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18
Q

What is bone remodelling?

A

opposing processes of bone formation and bone reabsorption

19
Q

What happens during bone remodelling?

A

Involves osteocytes dissolving and reabsorbing old bone and osteoblasts replace it with mineralised new bone - continual process of bone remodelling crucial for skeletal health
Osteoclasts from blood cell lineage reabsorb old bone
Osteoblast lay down new bone

20
Q

How is bone remodelling regulated?

A

This balance is controlled via the lifecycle and differentiation of these cells
Osteoclasts differentiate and undergo apoptosis in response to signals
Osteoblasts may terminally differentiate into osteocytes - remaining embedded in the matrix or differentiate into Lining cells - remain inert along bone surface

21
Q

Outline the phases of bone remodelling

A
  1. Activation
    - involves stimulation of osteoclast differentiation
  2. Reabsorption
    - governed by duration of action of the lifecycle of
    osteoclasts
  3. Reversal
    - involves signals terminating osteoclast activity and
    promote further osteoblast differentiation and coupled
    with osteoclast apoptosis
  4. New bone formation
    - basic multicellular unit
22
Q

What are the ways bone remodelling is controlled?

A

Load-bearing exercise
Cytokines and other local signals
Endocrine

23
Q

Explain how load bearing exercise effects bone remodelling

A

A noticeable decrease in bone density after just a week of hospital bed rest - easily reversed with resumed activity

24
Q

Outline how endocrine functions aid bone remodelling

A

Oestrogen: inhibits osteocyte apoptosis, promotes osteoclast apoptosis
Oestrogen is essential for skeletal health
Androgens

25
Q

What is RANK?

A

RANK (receptor activator of nuclear factor kappa-B): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation

26
Q

What is the RANK-ligand?

A

RANK-ligand: produced by pre-osteoblasts, osteoblasts and osteocytes; binds to RANK and stimulates osteoclast differentiation

27
Q

What is OPG?

A

OPG (osteoprotogerin): decoy receptor produced by osteocytes

28
Q

What is the role of OPG?

A

binds to RANK-L, preventing activation of RANK - competes for RANK ligand with RANK receptor - acts as a break of osteoclast differentiation

29
Q

Describe the significance of OPG in treating osteoporosis

A

Osteoporosis - decreased bone density associated with ageing

Treatment - Drugs promoting formation > reabsorption ie. inhibiting osteoclast activity and promoting osteoblast

30
Q

What is the Wnt signalling pathway?

A

Complex signal pathway, Required for osteoblast differentiation, highly conserved, involved in animal development

31
Q

How is the Wnt pathway mediated?

A

Negatively regulated by proteins: DKK (dickkopf) and sclerostin (SOST)

32
Q

What is Wnt?

A

Wnt is a signalling protein molecule that binds to its receptor (Frizzled) which requires a co receptor (LRP5/R)

33
Q

Explain the Wnt Signalling pathway

A

In presence of LRP5/R and Frizzled, Wnt can bind and activate its receptor causing ꞵ-catenin protein to be released and act as a TF promoting differentiation pathways

34
Q

What is the effect of DKK and SOST on the Wnt signalling pathway?

A

DKK1, and SFRP1 all inhibit Wnt signaling and subsequent osteoblast activity

35
Q

What proteins activate bone remodelling?

A

Osteocytes express RANKL and macrophage-colony stimulating factor (M-CSF) to promote bone remodelling via osteoclast formation and activity

36
Q

What inhibits new bone formation pathway?

A

OPG and NO inhibit osteoclast formation and activity

37
Q

How do osteocytes regulate remodelling?

A

Osteocytes also regulate bone formation via the secretion of modulators of the Wnt signaling pathway

38
Q

What factors stimulate Wnt pathway?

A

PGE2, NO, and ATP act to activate Wnt signaling, whereas sclerostin

39
Q

What is the significance of the Wnt pathway?

A

Maintenance of this balance between resorption and formation by the osteocyte is essential for bone homeostasis

40
Q

What is Rickets?

A

Essentially due to Vit. D deficiency (Vit. D one of major endocrine factors for bone mineralisation, failure causes rickets - bone is soft not brittle)

41
Q

What gene mutations cause diseases of bones?

A

Mutations affecting key signals
Very rare, but have elucidated mechanisms

Less rare: Osteomalacia
Common: Osteoporosis

42
Q

Describe the causes of osteoporosis

A

Osteoporosis pseudoglioma
Inactivation of LRP-5, wnt co-receptor
In children causes very poor bone development
Become severe osteoporosis - fracture prone
Can cause blindness due to retinal development failure

43
Q

What is Sclerosteosis?

A

Sclerosteosis and van Buchem disease
Mutation of SOST gene, inactivating sclerostin protein, Wnt pathway promoted - excess bone formation
Varying severity excess bone mass - heavy bone formation
Very high bone mineral density - associated physical features
Use linkage analysis to track GOI

44
Q

What is osteopetrosis?

A

Mutation inactivates RANKL protein

Prevents bone reabsorption

MSS & Skin (6 decks)

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