Biochemistry of bone formation Flashcards
(23 cards)
what molecules are involved in the control of osteoblastic proliferation and differentiation?
PTH
glucocorticoids
Why
TGFB
hedgehog
BMP’s
FGF
IGF
what is the key trigger for the formation of new osteoblasts?
expression of a molecule called cbfa1 in the pre osteoblasts
what is cbfa1?
a transcription factor that activates the coordinated expression of genes that are characteristic of the osteoblast phenotype such as osteocalcin, type 1 collagen and alkaline phosphatase
what happens when there is an activating mutation of LRP5?
high bone mass syndrome
what happens when there is a reduced sclerostin?
sclerosteosis/ van buchem disease
what are some systemic hormones that stimulate bone remodelling?
PTH
1,25 dihydroxyvitamin D
growth hormone
thyroid hormone
what are some locally acting factors that stimulate bone remodelling?
interleukin-1
tumour necrosis factor
interleukin-6
prostaglandins
what are some systemic hormones that inhibit bone remodelling?
oestrogens
androgens
progesterone
calcitonin
what are some locally acting factors that inhibit bone remodelling?
osteoprotegerin
mechanical loading
interferon gamma
interleukins 4,10,13,18
which period is critical in establishing bone health?
adolescence
what happens to the spine during adolescent changes?
increase size and trabecular thickness
what happens to long bones during adolescent changes?
increased length and diameter
what does the body produce to neutralise the effect of RANK ligand and defend against bone loss?
OPG
OPG, a natural endogenous inhibitor of RANK Ligand, acts as a decoy receptor by binding with RANK Ligand, thereby inhibiting osteoclastogenesis. 1,2
OPG, a member of the TNF receptor family, binds to RANK Ligand and neutralizes its effects, thereby inhibiting bone resorption.1,2,6
what does the drug denosumab do?
the first fully human monoclonal antibody that specifically targets RANK ligand and therefor inhibits osteoclast formation, function and survival
what is the most widely used method for searching or osteoporosis susceptibility genes?
candidate gene approach
what are the determinants of peak bone mass?
lifestyle
genetics (60-80%)
hormones
nutrition
what is the candidate gene approach?
involves typing markers that are concentrated near genes of interest. While these studies are generally more practical than linkage analyses in confirming an osteoporosis gene, they are also prone to giving false–positive results
what genes have been thought to contribute to OP?
transforming growth factor beta 1 (TGFBq) gene
what is associated with oestrogen deficiency?
increased osteoblastogenesis
increased osteoclastogenesis
increased lifespan of osteoclasts, reduced lifespan of osteocytes
what are some biochemical markers of bone turnover?
bone matrix components
-released in blood stream during formation and resorption
enzymatic activity
-specific for osteoblasts and osteoclasts
what are some formation markers?
Serum total alkaline phosphatase (ALP)*
Serum bone specific alkaline phosphatase (BSAP)
Serum procollagen I carboxyterminal propeptide (PICP)
Serum procollagen type 1 N-terminal propeptide (PINP)
Bone sialoprotein*
serum osteocalcin
what are some resorption markers?
Urinary hydroxyproline (Hyp)
Urinary total pyridinoline (Pyr)
Urinary total deoxypyridinoline (dPyr)
Urinary free pyridinoline (f-Pyr, also known as Pyrilinks®)
Urinary free deoxypyridinoline (f-dPyr, also known as Pyrilinks-D®)
Urinary collagen type I cross-linked N-telopeptide (NTx, also referred to as Osteomark)
Urinary/serum collagen type I cross-linked C-telopeptide (CTx, also referred to as Cross Laps®)
Serum carboxyterminal telopeptide of type I collagen (ITCP)
Tartrate-resistant acid phosphatase*
Urinary hydroxyproline (Hyp)*
what his sclerostin?
inhibit Want signalling in cells near the surface
the inhibition can result in release of stroll cells
