bs2 mod 3 Flashcards
What forms appendicular skeleton
Lateral plate mesoderm
Describe osteogenesis
Making of bone. Start out with BMP stim of Runx (then TRAF6) leading to progenitor to diff into osteoprotenitor. Then osterix leads it to differentiate into osteoblast. The ones that get trapped become osteocytes. The ones that don’t differentiation become periosteum and endosteum
periosteum layers
Fibrogenic outer layer with BP and sharpens fibres (extension of tissue into bone)
Osteogenic inner
bone formation
collagen deposition (steel bars) then ground substance made then seeding where ground substance saturated with Ca and P and precipitate out then mineralization when crystals are tethered to collagen by proteoglycans that give bone strength
Describe osteoclastogenesis
MCSF binds to monocyte to make macrophage.
Start out with MCSF stim on osteoblast?? RANKL made by osteoblast, t cells and MSCm chondrocytes too. Binds to RANK on monocyte to turn it into osteoclast
type 11 collagen
Type 11 is minor that attaches to type 2
Describe chondrogenesis
mesenchyme prolif and condense to prechondrocyte (signal by TGFb and WNT) then mature and hypertrophy to make room for vascular invasion
where do you find hyaline cart
respiratory passage, larynx, nose, articular surface of bones, ventral ends of ribs
Transient: skeleton model, epiphyseal growth plate
Sox9 mutation:
campomelic dysplasia
controls type 2 coll and aggrecan so autosomal dominant and bad. Bowing and angulation of long bones (sock shape) and Craniofacial abnormality
when does posterior fontanelle close
3 mos
intramem ossification
Mac to prolif and condense then diff to osteoblast via BMA stim of RUNx2. Vascular invasion via VEGF then form ossification centre
*priosteum is fiber layer where vascular MSC condense
starts in suture lines and periosteum from progenitor cells
endochondral ossification
Msc prolif then chondrocytes make type 2 collagen, then FGF and RUNX2 make hypertrophy then VEGF
- MSC to prechondrocyte is TGFb and want
- Prechondrocyte to chondrocyte is sox9 (disorder is campomelic dysplasia)
- Starts from growth plates and end plates from chondrocytes
Vascular growth plate makes what
type 1 coll
process of bone width growth
Width bone growth: periostea ridge pinches off to form endosteum that grows out by secreting matrix and forming lamella by making type 1 fibres
appositional is where bone resorbed in thick area to add to thin area
What does thyroid hormone do to bone growth
DELAYED
activation of bone remodelling
activation (recruit osteoclast) to resorption then reversal (osteoclasts die and osteoblast recruited) then formation/mineralization
osteocyte control
Cites make OPG and NO to stop osteoclast. Stim osteoclast by making MCSF and RANKL
runx mutation
Cleidocranial dystosis
- messed up collarbone, open fontanelle
- teeth
osterix mutation
osteogenesis imperfecta
b catenin does what
Regulates osteoclastogenesis since controls osteoprotegin and RANKL on osteoblast
TGFb signal
tgfb is stored in ECM. Binding turns on canonical and non canonical. Stops osteoblast progenitor and makes osteocyte instead
how does indian hedgehog work
Allows osteoblast prolif by increasing Runx2 and sox. Inhibited by PTCH
what does FGF do
regulate both endochondral and intramem ossification by control osteoblast prof, diff and APOPTOSIS
turns on Runx
What happens in RANKL mutation?
Mutation causes pages disease: bone bending, tooth loss. Too much osteoclast
OPG mutation is juvenile pages where suture problem effects osteoblast diff (OBGYN = baby)
What are proinflammatory factors vs inflammatory and what do they do
ROS in age, proinflam induce OC Diff (TNFa, Il1 and Il6) and antiinflam does inhibit of OC (il 4, 10, IFN a and IFN b).
ca release from ER
IP3 then ca out then protein kinase c then calmodulin
Which organs/cells have PTH receptors
Receptor is PTH1R is mostly on kidney and bone!! Also in growth plate chondrocytes!
which organs have serum ca sensing receptor
Serum Ca sensing receptor is GPCR. ON parathyroid and c cells of thyroid. Also in kidney, chondrocytes and osteoblasts
catabolic and anabolic functions of PTH
catabolic PTH: high PTH means promote osteolysis using higher RANKL
Anabolic: low PTH is 4 stage: promotes RUNX2 and osx to diff to osteoblast. Sclerotin is the wet inhibitor so decrease it to promote bone formation
Describe calcitonin structure
32 AA peptide. No diff if its taken out on ca homeostasis!
Describe the PO4 levels in the body
Po4 normal level is 3.0 to 4.5 mg/dl. 87% is diffusible with 35% completed to diff ions and 52% ionized.
13% is non diffusible protein bound. 85-90% is in bone.
progenitor, unipotent, differentiation and specialized cells
Progenitor is terminally diff
Unipotent is self renewal Postnatal or adult
Differentiation is specific function
Specialized cells are DIFF NOT DIVIDING
DPSC< SHED< SCAP< PDLSC< HODSC
DPSC make dentin
SHED is prolif
SCAP is apical. NEURAL
PLSC is PDL and cementum
HODSC is human odontoma. Does dentin and pulp
chondrocyte diff factors
TGFb, BMP and WaNt control chondrocyte diff
which bmp factors are osteoinductive
2,4, and 7
sphenoid bone origin
Wings of sphenoid are neurocranium, while body is mesodermal sclerotome! (Back of head)
how does palate form
cortical drift? deposition of bone on oral side, resorption on nasal side. Creates the maxillary tuberosity and alveolar process
middle mechels cart becomes
middle is sphenmand ligament
mand vs max growth
- first grows width, length then height through bone remodelling
max: Down and out sutural growth
Median palatine suture
is important for transverse growth of maxilla —> expander thing
Median palatine suture
is important for transverse growth of maxilla —> expander thing
p and vit d levels in renal osteodystrophy and osteomalacia
Describe renal osteodystrophy
increase serum phosphate, no vit D
Describe tumor induced osteomalacia
phosphate wasting, abnormal vit D meta
3 stim of bone formation
PTH 1-34 (teriparatide), strontium ranelate: dual action on osteoblast and class, anti-sclerostin (evenity): stim wnt
All are osteoblast stim
What are the 5 bone resorption inhibitors
Cold BEER
Cathepsin inhibitor, bisphosphonate (ends in -onate), estrogen and estrogen mimic, RANKL antibody (most effective, only 2 injection per year)
denosumab
limits rank interaction and decrease osteoclast formation
Odanacatib
cathepsin inhibitor): stop bone matrix degradation
Most strong since stop bone loss and also increase bone formation!
where do bisphosphonates inhibit
acetyl coa merges with acetyoacetyl coa to make geranyl PP INHIBIT THE FARNESYL DISPHOSPHATE SYNTHASE (SO NO FARNESYL PP)
No cholesterol or isoprenylation (essential to osteoclast)
Describe ONJ histologically
empty lacunae and ragged border
bevacizumab
anti VEGF, less blood invasion
sunitinib
tyros kinase inhibitor
radionecrosis pic
Cells look less pink, more white
Strain
deformation and is dimensionless measure of shape change (length and angle)
Stiffness
measure of how stress and strain. Change in stress required for change in strain
slope of stress strain curve
viscoelastic bone property
Rate of force applied. Slow rate is more high fracture!!!
anisotropic bone quality
Direction of load. Cancels is for bending, cortical is for compressive! (Less marrow)
Good for longitudinal force, not transverse
aging in bone
Increase resistance to torsion but less to compression
Wider marrow hole thing
Bone healing
need GIRLS CAN PLEASE VERY HORNY GUYS
Growth factors, cytokines, prostaglandins/leukotriens, vascular factors, hormones, GF antagonist
fracture steps
hematoma, fibrocart callous, bony callous then remodelling
Hematoma fracture
6-8 hours
Fibrocart callous
3 wks: hematoma is granulated into pro callous then fibroblast and osteogenic cells invade. Form collagen fibres to connect ends then hondroblast begin to produce fibrocart
Bony callous
after 3 weeks, lasts 3-4 months. Osteoblasts make woven bone
** callous is internal spongey bone but also external in cart!
lamina dura and pdl
Lamina dura is opaque and PDL is Lucent
odontoma
Big radiopacity
mucous cyst
Easily seen in CT ?? scan due to radiographic contrast
Hyperparathyroidism radiograph
increased bone resorption
Adenoma tumor can cause primary increase in PTH
Secondary is chronic renal failure so low ca meaning more PTH
More broken bones
Salt and pepper appearance or tumors
Radionuclide diagnosis: #bug
Hypothyroidism radiograph
missing bones
Acromegaly
too much growth hormone so big organs/head random parts
gigantism is height overall big
pet scan markers
Red light thing fluorodeoxyglucose FDG and NAF (bright light) as markers
progenitor cell differentiation
- fibrous dysplasia
gnas, gra, mono or poly,
MORE in mand and max - mas syndrome
- bendy
can be cancer - lion tarsus ossea
- bad maturation of bone cells
ossification disorder
achondroplasia
- bad FGFR disorder
- no cart growth trigent
pagets disease
- many factors like runx2 and osx (juvenile)
- no osteoclast diff, more resorption, weak holy bone
- higher alp weird pee thick skull
- whiter jaw bone
remodelling bone defect
osteopetrosis
- cfos/mos gene
0 brittle bone with less osteoclast
- white skull
- anemia stuff
ECM problem
- COL1a gene osteogenesis imperfecta
- JEEST so joints, eyes, ears, skin, stiff, teeth
- osterix problem
- messes up endochondral
- dentinogenesis imperfecta
- type 1 collagen
- 1st is nondeforming and messes up quantity
- 2-4 is deforming and mess up structure
mineralization disorder
- hypophosphatasia
- less alp so lethal
- tooth loss, more big pulp chamber
- no bone mineralization
- beaten copper frontal bone
transverse, linear fracture
perp and parallel
oblique displaced and non
moved by muscle
spiral and greenstick
spiral is torsion and greenstick is surface
comminuted
many places fracture
