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Terms in this set (63)
What type of tissue is bone?
Why is bone considered a connective tissue?
It is made up of a small proportion of cells and a large proportion of matrix
What is meant by bone dynamics?
Bones are continually reshaped to maintain the right amount of healthy bone tissue in response to levels of stress in a particular area
What happens if a bone is under-stressed for a prolonged period?
Bone wastage occurs
Bones become thinner
Why might a bone be under-stressed?
E.g. if a patient is bed-ridden for a long time
What happens if bones are suddenly subjected to high levels of stress?
Increase in bone mass
Why might bone by under sudden stress?
E.g. new recruits to the army (intense training)
The functions of bones
Mineral (calcium storage)
Hematopoiesis (produces blood cells in bone marrow)
(look at notes for better diagram)
Outer hard casing -- cortical bone
Innter trabecular bone
Accounts for 80% of the total mass of the adult skeleton
Has a dense, more regulated structure and forms the thick-walled tube of the shaft or diaphysis of long bones
Surrounds the marrow cavity (or medullary cavity)
A thin layer also covers the epiphyses of long bones
Also called spongy/cancellous bone
Consists of delicate bars and sheets of bone (trabeculae)
These branch and intersect to form a sponge like meshwork
The ends of the bone
Contains mostly trabecular bone
An outer layer of dense connective tissue
A thin layer of cell-rich connective tissue
Lines the surface of the bone facing the marrow cavity
Which layers posses osteogenic potency?
Periosteum and endosteum
Following injury, cells in these layers may differentiate into bone to ai repair
Functions of the periosteum
Acts as an anchoring point for tendons and ligaments
Direction of bone strength
High compressional and tensile strength
Low level of torsional strength
(and so fractures often occur as a result of torsional forces exerted on an upper or lower limb)
What gives bone its high compressional and tensile strength?
Types of bone cell
These are the stem cells of bone
Located in the periosteum and endosteum
Differentiate into osteoblasts
Bone producing cells
Sometimes form a low columnar "epitheloid layer" at site of bone deposition (almost like an epithelium)
Differentiate into osetocytes as they become trapped in the forming bone
Located in lacunae
Connect with each other through canaliculi
What are lacunae?
Small cavities in bone
(cyte -- from greek meaning hollow)
What are bone canaliculi?
Small channels between lacunae
Very large (up to 100µm)
Multi-nucleate bone-resorbing cells
Arise from macrophage precursors in the blood
(clast-- meaning broken)
What acts as an intrinsic method to regulate bone growth?
When osteoblasts become surrounded by bone they become osteocytes (quiescent)
What is bone made up of?
Relatively few cells (mostly osteoblasts and osteocytes)
A mineralised matrix containing collagen fibres
Organic component of the bone matrix
Collagen fibres (95% type I)
Amorphous material (inc glycosaminoglycans that are associated with proteins)
What confers the tensile strength of bone?
Inorganic component of the bone matrix
Represents 50% of dry weight of matrix
Calcium and phosphate
Smaller amounts of bicarbonate, citrate, Mg, K, Na
Calcium forms hydroxypatite crystals with phosphorus (also present in other forms)
Calcium salts confer compressional strength
Collagen fibres in compact bone
Alligned collagen fibres
Laid down by osteoblasts around the tunnels created by osteoclasts
Form concentric arrays of lamellae -- an osteon
When this surrounds an initiating blood vessel in the Haversian canal it is called a Haversian system
What is osteogenesis imperfectia?
A group of inherited diseases associated with mutations affecting type I collagen genes (COL1A1 or COL1A2)
Null mutations cause less type 1 collagen to be produced (milder form)
Dominant-negative mutations interrupt the triple helix of collagen by adding a large amino acid in the wrong place
Causes brittle bones that break easily, often with little or no apparent cause
What is osteomalacia?
A loss of skeletal mass caused by inadequate mineralisation of the normal osteoid tissue after the closure of growth plates
Softening bones so bowing of legs
Looser's zones may appear (incomplete fractures filled with un-mineralised osteoid seams
In children this is known as Rickets
(both caused by a deficiency of vitamin D)
X-rays show decreased bone density
What are green-stick fractures?
The bone breaks incompletely (one side of the shaft breaks and the other bends)
Common in children because their bones have relatively more organic matrix and are more flexible than adult bones
Two mechanisms of bone formation
Which bones are formed by intramembranous ossification?
Bones of the skull
Part of the mandible
Lateral end of clavicle
What exists before endochondrial ossification?
This is formed by condensation of mesenchyme into chondrocytes which form a cartilage 'model' of the bone
What is the first step in endochondrial ossification?
Hypertrophy (swelling) and death of chondrocytes in the centre of the cartilage (at primary ossification centre)
This enables the invasion by blood vessels which allows osteoprogenitor cells to enter the cartilage
Differentiate into osteoblasts and secrete osteoid
This whole process is associated with expression of osteocalcin
What is osteoid?
The unmineralised organic ECM that binds calcium
What is the original arrangement of collagen fibres?
Haphazard (woven bone)
Temporal sequence of ossification
More proximal structures begin ossification earlier
Metacarpals and phalanages later
In what direction does ossification occur within a bone?
Starts in the centre of the bones and spreads to the ends
What is the differentiation of osteoblasts dependent on?
Runx2 and Osx2 (osterix)
Both required for normal ossification
Function of Runx2
Essential in generating 'preosteoblasts'
Stimulating Osx2 production
Function of Osx2
Downstream of Runx2
Represses Sox9 to favour the osteoblast pathway over the chondrocyte pathway
(slides for diagram)
What do defects in Runx2 lead to
Often a defect in the clavicle (failure of ossification)
Where is the secondary ossification centre?
In the epiphysis
What remains as cartilage between the epiphysis and diaphysis?
Epiphyseal growth plate
Zones of the cartilaginous cells in the epiphyseal growth plate
Quiescent zone/stem cells
Proliferative zone of cell division
Ossifying cartilage (becoming diaphysis)
There is a transition to bone where cartilage cells die (replaced by osteoblasts)
Hypertrophic zone is closest to the diaphysis
What promotes this process?
IHH (indian hedgehog) expressed in the proliferating cells
Acts to promote proliferation and prevent hypertrophy
Growth hormone, thyroid hormones, IGF1 (probably act . on the germinal zone stem cells) -- therefore by both local and systemic control
What occurs in African Pygmies?
IGF1 levels during puberty drop to 1/3
Resistance to GH
What inhibits growth?
Inhibits growth and promotes differentiation
FGF3R is present in chondrocytes
What condition is associated with an activating mutation in FGF3R?
Constant inhibition of growth by over-active FGF3 pathway
When does the growth plate ossify?
At the end of puberty
What is bone remodelling needed for?
Making compact bone
Response to mechanical stress
Removal and replacement of ageing bone
Repair of fractures
Account for 15% of childhood fractures
Twice as frequent in boys because girls finish ossification earlier
What is the role of osteoclasts in bone remodelling?
Cling to bone matrix and erode it
Tunnel deep into the matrix to form cavities
(diagram in slides-- probably should print off)
What regulates osteoclasts development?
Cytokines and RANKL (RANK ligand)
RANKL promotes osteoclast acitivity
Osteopregin (OPG) acts as a decoy receptor by binding with RANKL and inhibits osteoclast activation
Calcitonin inhibits osteoclastin when Ca++ is high
Parathormone (PTH) stimulates osteoclasts when Ca++ is low
Other stimulators of bone resorption (PTH, IL-1) increase osteoclast formation by stimulating production of RANKL
How does bone remodelling create compact bone?
Groups of osteoclasts form a cutting cone
Followed by osteoblasts which deposit new osteoid matrix concentrically around a central ingrowing blood vessel
Pattern and extent of modelling dictated by mechanical loads
What occurs in osteoporosis?
Means porous bones
Bone resorption>bone formation
Bones become fragile and susceptible to fracture
An adequate supply of calcium in early adulthood needed to prevent this
About 20% of women over 50 have low bone density
Paget's Disease of Bone
Excess activity of osteoclasts
Leads to a lot of woven bone (at the expense of compact bone)
Can be familial -- many linked to mutations in RANK and OPG
4 Stages in bone repair
1. Inflammation and formation of hematoma
2. Foramtion of fibrocartilage callus
3. Replacement of cartilage with lamellar bone
4. Remodelling bones to normal contour
(diagram in notes)
Which factors affect bone healing?
Poor blood supply
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