Bone biology Flashcards
What are the components of bone?
Organic component:
–> osteiod:
90% Type 1 collagen
10% GAGs (glorified polysaccharides)
Inorganic component:
–> hydroxyapatite= Ca10(PO4)6(OH)2
Key cells of bones
Osteoprogenitor- ‘founding fathers’ precursor for osteoblasts
Osteoblast- Bone makers. Few in number, precursor to osteocytes
Osteocytes- Bone cells which maintains the ECM
Osteoclasts- The bone Resorbers. Formed from pro-monocyte cell lines.
Function of alkaline phosphatase
- Important enzyme produced by osteoblasts
- Splits 1 pyrophosphate into 2 phosphates
- -> inc. [phosphate]
- -> more phosphate binds with calcium
- -> more calcium phosphate and so more hydroxypatite
- -> more bone precipitation
- -> helps osteoblats form bone
Osteoclast activation
- PTH is secreted in response to low blood calcium
- PTH binds to osteoblast receptors
- Osteoblast has RANKL on CSM, Osteoclast precursor has RANK
- Binding of RANK-RANKL activates osteoclasts
Osteoclast action
- contain high amounts of carbonic anhydrase–> high amount of H+ to be released
- Secretion of Cathepsin K (protease) –> breaksdown collagen in bone at pH5.
Action of Sclerostin
- Secreted by osteocytes
- Sclerostin ‘ain’t got time’ for bone formation.
–> It INHIBITS bone formation by blocking RANK receptor (blocks bone remodelling pathways)
Bone remodelling pathways
- Osteocytes are mechanosensory- they sense load on the bone
- Osteocytes signal for osteoclast maturation and differentation
- Osteoprogenitors for osteoblast- which produce osteoid
- Calcification of bone matricx with hydroxypatite occurs over 6 MONTHS
- Bone ‘adapts’ and strengthens to mechanical load.
What are the normal ranges of calcium in the blood?
2.2- 2.5 mmol/L
Consequences of hypercalcaemia
Cardiac arrest and Coma
Consequences of hypocalcaemia
Tetany- hand spasms
Vit D pathway
- Sunlight converts 7-Dehydrocholestrol into Vit D3 (Cholescalciferol)
- In the liver, Vit D3 is converted into 25-OH D (hyroxylation)
- In the Kidney, 25-OH D converted into 1,25-OH D
Increasing Calcium in the Blood: Vit D (Calcitriol)
- Promotes Ca2+ absorption from small intestine
- Causes bone to lose calcium
(Vit D increases phosphate in the blood)
Increasing Calcium in the Blood: PTH
–> Causes bone to lose calcium (signalling pathway to increase osteoclastic activity)
–> Causes kidney to absorb more calcium (see UG block)
(PTH increases phosphate excretion in the kidneys)
Decreasing Calcium in the Blood: Calcitronin
- Produced from parafollicular cells
- Inhibits osteoclasts (no bone resorption
- Inhibits calcium absorption in small intestine
- Inhibits calcium reabsorption at kidneys
Collagen formation
- Pro-collagen is formed in the cells (trial helix structure–> 1 alpha and 2 beta chains)
- Pro- collagen is secreted into ECM
- Pro-collagen is cleaved at N and C terminal, giving final collagen molecule
- Collagen molecules link to form fibrils
