Lecture 27 - Healthy Bone Flashcards
Cortical bone is the ___ layer
outer
Cancellous (trabecular) bone provides structural integrity __ the bone
inside
Collagen is___ of adult bone mass
10%
_________ is the major mineral in bone
Hydroxyapatite - insoluble salt of Ca and phosphorus = 65% of adult bone mass
Water accounts for __% of bone mass
25%
about ___% of our bone is replaced each year
5-10% - bONE REMODELLING
Bone remodelling is initialted ________ throughout the skeleton
asynchronously
bone provides __ of the bodys calcium
99% of Ca and 85% of phopshorus
Bone is resorbed to release _____ into blood when required
calcium
what else does bone remodelling allow?
adaptation of shape in resposne to biomechanical movement
repair of microdamage
osteoclasts resorb bone leaving ____ _____
Osteoblasts then fill in that space, making _____
osteoclasts resorb bone leaving resoption cavities
Osteoblasts then fill in that space, making Osteoid (un-mineralised bone) - they eventually get mineralised
Osteoctyes are embedde in the ___ ____
bone matrix- critical for controlling bone remodelling
Trobecular can become thinnerover time, causing…
osteophorosis - bone is more likely to fracture
Net bone gain can be called..
Osteopetrosis
Osteosclerosis
High bone mass
osteoclasts are Large _____ cells, enriched with ____
osteoclasts are Large multinucleated cells, enriched with mitochrondria (to use energy to resorb bone)
set through how osteoclasts resorb bone:
1) Forming a ‘sealing zone’ by intergin-mediated attachment to bone
2) acidification of resorptive lacunae to dissolve the mineral component
3) Release of callagenases and other enzymes to degrade the organic component
4) Bone degradation products are taken up by the osteoclasts and released
The process of bone resorbtion takes about
3 weeks
osteoblasts stem from a ______ skeletal stem cell
osteoblasts stem from a mesenchymal skeletal stem cell
also differentiate to muscle cells
Following cessation of osteoprogenitor proliferation, osteoblasts:
secrete _____proteins (osteoid) including ____, bone ______, _______
express ______phophatase
renders the osteoid competent for ______ _______
secrete ECM proteins (osteoid) including collagen, bone sialoprotein, ostecalcin
express alkaline phophatase
renders the osteoid competent for mineral deposition
How long is the bone forming process?
3-4 month long
osteoclast are from a _______stem cell precursor
osteoclaast are from a haemopoetic stem cell precursor
common with macrophages
RANKL (provided by osteoblasts) will bind to ___ (on osteoclast precursors) and promote bone-resorbing
RANKL will bind to RANK (on osteoclast precursors) and promote bone-resorbing
Osteoblasts can also provide an inhibtor to RANKL called
OPG - decoy receptor
If you take RANKL away, the osteoclasts will..
die
Mice with RANK-/- develop severe
osteophorosis
The negative inhibitor for RANKL is
OPG - Osteoprotegerin
True or False
OPG is structurally distinct from RANKL
true
_____ is the essential cytokine required for osteoclast differentiation, survival and fucntion
RANKL
__ligands promote osteoblast differentiation and function
Wnt
Wnt signals through Beta-catenin - to act on gene transcription to help..
Osteoblasts bone formation
Wnt ligands are soluble factors that act by binding the co-receptors ____and _____ or _____
Wnt ligands are soluble factors that act by binding the co-receptors Frizzled and LRP5 or LRP6
This results in stabilisation of the signalling intermediate beta-catenin within the cytoplasm
B-catenin participates in gene transcription causing…
osteoblast differentiation
can aso inhibit osteoclast differentiation
What are the inhibitors of the Wnt signal pathway?
sFRP-1
DKK-1
Sclerostin
which out of
sFRP-1
DKK-1
Sclerostin
interact with Wnt ligands and which affect the co-receptor complex?
DKK-1
Sclerostin
- prevent Wnt signalling by bindLRP5 or LRP6 preventing these coreceptors from interacting with Frizzled
sFRP-1 inhibits by binding to Wnt ligands themselves
The most abundant bone cells are the
Osteocytes 20-25 yrs
osteocytes sit within the bone matrix in ____
lacunae
osteoctyes express both ____and___ as a means to regulate bone formation
osteoctyes express both sclerostin and DKK-1 as a means to regulate bone formation
Bisphophoantes inhibit
osteoclast activity
Anti-RANKL antibody inhibits
osteoclast differentiation and survival
___ 1-34 acts to increase the maturation of osteoprogenitor stem cells as well as sclerostin and DKK1
rpPTH 1-34 acts to increase the maturation of osteoprogenitor stem cells as well as sclerostin and DKK1
