RA - L3 Flashcards
Composition of bone
organic matrix (90% collagen)
minerals: hydroxyapatite (insoluble salt of calcium and phosphorus - 65% of bone mass)
water: 25% of bone mass
Why is bone remodelled?
maintain mineral ion homeostasis
adapt shape and structural organization to alterations in biomechanical force
repair microdamage
Describe the bone remodelling process
osteoclasts resorb a section, leaving a resportion cavity
osteoblasts fill the resorption lacuna and start laying down collagen (called osteoid)
osteoblasts leave and mineralisation of osteoid takes plce
resportion - 3 weeks
formation - 3-4 months
Describe osteoclast bone resorption
form sealing zone by integrin mediated attachment
acidify resorptive lucanae to dissolve mineral component
release collagenases and other enzymes to degrade organic component
bone degradation products taken up by osteoclast and released
Osteoclast differentiation
haemopoetic stem cell
myeloid precursor cells (same for macrophages)
osteoclast precursor cell (by macrophage-CSF)
What happens if too much RANKL?
net bone loss
What happens if too much OPG?
net bone gain
Where does RANKL come from in healthy bone?
osteoblasts
Where do osteoblasts come from?
mesenchymal stem cells
Osteoblast ECM proteins released?
collagen
sialoprotein
osteocalcin
What does alkaline phosphatase do?
released by osteoblasts, primes osteoid for mineralisation
What promotes osteoblast differentiation?
Wnt ligands
Describe the Wnt pathway
Wnt ligands bind frizzled & LRP5 or 6
b-catenin stabilzation
b-catenin activates gene transcription –> osteoblast diff.
b-catenin can also promote OPG expression
Name some Wnt antagonists
DKK-1
sclerostin
sFRPs (bind Wnt ligands directly)
What do osteocytes do?
respond to mechanical stress by decreasing bone formation by releasing sclerostin and DKK-1 and RANKL
