MSS: Cellular Structure of Bone Flashcards by aimen n

Outline the functions of bone

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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Describe the 2 types of bone structure

Cortical (compact) bone

Trabecular (spongy, cancellous) bone

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What is the composition of bone?

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

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

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

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Name the common bone minerals

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

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What is the purpose of bone minerals?

Rigid, brittle: gives high compressive strength

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Name examples of bone cells

Osteoblasts
Osteoclasts
Osteocytes

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What are the bone marrow cells?

Mesenchymal (stromal) stem cells

Haematopoietic stem cells

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What are osteoblasts?

Bone forming cells derived from mesenchymal stem cells

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What is the function of osteoblasts?

Secrete osteoid, collagen matrix of bone

Promote mineralization of osteoid

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What are osteoclasts?

Large, multinucleate bone reabsorbing cells derived from haematopoietic stem cells

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How is the osteoclast lifecycle mediated?

Life cycle controlled by apoptosis

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What is the role of osteoclasts?

Secrete acid to dissolve bone mineral

Secrete enzymes to digest organic matrix

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What are osteocytes?

Terminally differentiated osteoblasts

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

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Describe the structure of osteocytes

Encased in bone mineral matrix (lacunae)

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

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Outline the function of osteocytes

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

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Where does bone remodelling occur?

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

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What is bone remodelling?

opposing processes of bone formation and bone reabsorption

What happens during bone remodelling?

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

How is bone remodelling regulated?

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

Outline the phases of bone remodelling

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

What are the ways bone remodelling is controlled?

Load-bearing exercise
Cytokines and other local signals
Endocrine

Explain how load bearing exercise effects bone remodelling

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

Outline how endocrine functions aid bone remodelling

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

What is RANK?

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

What is the RANK-ligand?

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

What is OPG?

OPG (osteoprotogerin): decoy receptor produced by osteocytes

What is the role of OPG?

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

Describe the significance of OPG in treating osteoporosis

Osteoporosis - decreased bone density associated with ageing | Treatment - Drugs promoting formation > reabsorption ie. inhibiting osteoclast activity and promoting osteoblast

What is the Wnt signalling pathway?

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

How is the Wnt pathway mediated?

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

What is Wnt?

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

Explain the Wnt Signalling pathway

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

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

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

What proteins activate bone remodelling?

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

What inhibits new bone formation pathway?

OPG and NO inhibit osteoclast formation and activity

How do osteocytes regulate remodelling?

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

What factors stimulate Wnt pathway?

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

What is the significance of the Wnt pathway?

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

What is Rickets?

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

What gene mutations cause diseases of bones?

Mutations affecting key signals Very rare, but have elucidated mechanisms Less rare: Osteomalacia Common: Osteoporosis

Describe the causes of osteoporosis

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

What is Sclerosteosis?

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

What is osteopetrosis?

Mutation inactivates RANKL protein | Prevents bone reabsorption