Bone metabolism Flashcards
What is the main type of collagen found in bone matrix? What is its role?
Collagen type I (main component of organic part of bone)
- tensile strength
What is the main component of the inorganic part of bone?
Calcium hydroxyapatite
What are the main bone cells? From where are they derived?
Osteoblasts + osteocytes are from osteoprogenitor cells (osteocytes are inactivated osteoblasts)
Osteoclasts are derived from the same cells that differentiate to form macrophages and monocytes (therefore have a haematopoietic cell lineage)
What is the role of osteocytes?
Osteocytes have many processes which pass through small channels int he bone matrix called CANALICULI
they indicate mechanical stress of the bone vie bend and stretch of the canaliculi
osteocytes are sensors for bone health and communicate when bone needs replacing
How long does it usually take for bone to be replaced/remodelled?
~3-6 months
How many osteoclasts are seen within bone at any given time?
If the bone is normal, it should be ~1-2 osteoclasts at once
How do cells know when bone needs replacing?
Death of osteocytes will signal remodelling for bone
- die when canaliculi break
- release sclerostin upon death
What is sclerostin? What does it do? What promotes and inhibits it?
it is a secreted glycoprotein
it inhibits osteoblasts and therefore inhibits bone formation
it is upregulated by calcitonin
it is inhibited by mechanical stress and PTH
How do osteoclasts resorb bone?
- Follow the signal produced by osteocytes and clamps down o this bone
- releases a mixture of acid and proteases
- -> acid dissolves calcium hydroxyapatite
- -> proteases break down breaks down collagen
- osteoclasts then take up the broken down material and transport it into the extracellular interstitial fluid
How do osteoblasts form bone?
- Come along after the osteoclasts and fill the lacuna with osteoid
- reuses the calcium and phosphate that the osteoclast put into the extracellular fluid to mineralise the osteoid
- osteoid is mineralised ~1 week later
What is normal serum calcium level?
2.2-2.6 mmol/L
What is the normal plasma phosphate concentration?
0.8-1.5 mmol/L
What changes occur when plasma Ca2+ is low?
- Low plasma Ca2+ concentration stimulates PTH secretion
- PTH promotes:
1. Ca2+ reabsorption and PO43- excretion from the kidney
2. Ca2+ reabsorption from bone (by increased number of activity of osteoclasts) - -> osteoblasts have a receptor for PTH causing them to produce RANKL
- -> osteoclasts and their precursors have RANK receptors
- -> indirect production of RANKL increases number of osteoclasts
- 1,25(OH)2 vitamin D3 increases Ca2+ absorption form the gut
- increased Ca2+ absorption from gut, kidney and bone
What are RANKL and M-CSF? What are their effects on osteoclasts?
RANKL: receptor activator of nuclear factor kappa-B ligand
- produced by osteoblasts and stromal cells
M-CSF: macrophage colony-stimulating factor
Both of these are required for osteoclast formation
What is OPG? What is its effect on osteoclasts?
OPG = osteoprotegrin
- it is a decoy receptor for RANKL
- when it is secreted it will bind to RANKL and stop signalling from osteoblasts
OPG inhibit osteoclast formation
