Cellular structure of bone Flashcards
What are the functions of bone?
- 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
What does the bone marrow do?
Produces blood cells and other types of stem cells
What part of the bone acts as a mineral reservoir?
Serum calcium (extracellular calcium) that is tightly regulated as an important mineral source for calcium and phosphate
Describe the two structures in bone
- Cortical (compact) bone
- Trabecular (spongy, cancellous) bone
What is cortical bone?
- 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
What are osteons?
Osteons are circular sheets or lamellae of bone matrix/tissue around central canals called Haversian canals
What do Haversian canals contain?
They contain blood vessels, nerves etc
What is trabecular bone?
- 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
What are the two typical types of bones?
- Long bone - Flat bone
What is the structure of long bones?
Composed of the head and the shaft
What is in the middle of the long bone?
Bone marrow filled cavity
Describe the normal composition of bone
- Protein: organic osteoid matrix (25%)
- Mineral (75%) - mixed with the osteoid matrix and is mainly calcium and phosphate + HYDROXYAPATATITE
- Cells
What is the composition of the organic protein matrix?
Mainly type 1 collagen
What is the purpose of the organic protein matrix (osteoid)?
- For flexibility and tensile strength - the strength of the bone resides here
What is tensile strength of bone?
The ability of bone to bend slightly to resistance the perpendicular forces (right angles).
What is the major component of bone mineral?
Hydroxyapatite
What are the other components of bone mineral?
Calcium and phosphate
What is the function of bone mineral?
Rigid, brittle and gives high compressive strength (longitudinally) which is important for the ability of the bone to bear load
What are the major bone cells?
- Osteoblasts
- Osteoclasts
- Osteocytes
What do the mesenchymal (stromal) stem cells differentiate into?
They give rise to osteoblasts
What is the function of osteoblasts?
Responsible for forming the organic matrix of bone and promoting the mineralisation
How are osteocytes formed?
The osteoblasts terminally differentiate and become osteocytes found within the bone matrix.
What do osteoblasts secrete?
The bone matrix and intune themselves encased inside the bone matrix
Where are osteoclasts found?
Found lining the inside of the cortical bone on the marrow cavity, large multi-nucleated cells and derive from the blood cell lineage
Summarise function of osteoblasts
FORM NEW BONE
- Derived from mesenchymal stem cells
- Secrete osteoid, collagen matrix of bone
- Promote mineralisation of osteoid
What do the osteoclasts do?
Bone reabsorbing cells
What do bone reabsorbing cells do?
- 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)
What is the most important proteolytic enzymes released by osteoclasts?
Cathepsin K that has a high affinity for type 1 collagen to dissolve bone and cartilage.
What are osteocytes?
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
What do the osteocytes coordinate?
They coordinate osteoblast (cells forming new bone) and osteoclast (cells that reabsorb old bone) activity
Define bone remodelling
The opposing processes of bone formation and bone reabsorption
What do the osteoblasts secrete and do?
They secrete osteoid which will mineralise and form new bone. This is bone recycling.
When do osteoclasts differentiate?
They differentiate in response to appropriate signals and then undergo apoptosis within a certain timeframe.
When do osteoblasts differentiate and what happens to them?
Osteoblasts will terminally differentiate into osteocytes and remain embedded in the matrix or remain inert along the bone surface
What are the four stages of bone remodelling?
- ACTIVATION = stimulation of osteoclast differentiation
- REABSORPTION = Duration of action of osteoclast
- REVERSAL = signals terminate osteoclast acitivity and promote further osteoblast differentiation, apoptosis of osteoclast
- FORMATION = formation of new bone
What controls remodelling?
- 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
What hormone is involved in bone remodelling?
Oestrogen inhibits osteocyte apoptosis and promtes osteoclast apoptosis.
- Promotes bone health
- Produced by aromatase
How is osteoclast differentiation induced by the rank ligand?
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
What does OPG do?
- decoy receptor produced by osteocytes; binds to RANK, preventing activation by RANK-L
What is the Wnt signalling pathway?
- 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.
What hormones will negatively regulate the Wnt pathway?
DKK (dickkopf) and sclerostin
What is the less rare disease of the bone?
Osteomalacia = weakening and softening of the bone, more prone to fractures due to failure of mineralisation
What is ricketts?
Soft bones like cartilage in children, due to vitamin D deficiency. It can occur in the elderly.
What is vitamin D required for?
It is an endocrine factor required for bone mineralisation.
What is a common bone disease?
Osteoporosis
What is osteoporosis?
loss of bone density, Increase in bone resorption over formation, increased fracture risk
What is the downfall of osteoporosis?
More prone to fractures, suffered by the elderly, can be attributed to the weakening of the bone.
What are some bone diseases caused by mutations?
- 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
What causes osteoporosis pseudoglioma?
Inactivation of LRP-5, WNT Co-receptor
What causes sclerosteosis and van Buchem disease?
Mutation of SOST gene, inactivating sclerostin protein so there is excess bone mass.
What causes osteopetrosis?
Mutation inactivates RANK-L protein. This prevents the reabsorption of bone.
Describe the loss of bone density correlation with ageing
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
